Overview of the role of vitamins and minerals on the kynurenine pathway in health and disease.

The kynurenine pathway (KP) of L-tryptophan metabolism produces several neuroactive metabolites with an amino acid structure. These metabolites may play an important role in the pathophysiology of irritable bowel syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, AIDS-dementia complex, depression, epilepsy and the aging process. Modulation of the KP through inhibition or stimulation of enzyme synthesis and activity can be an alternative approach to traditional therapy. Furthermore, it may be responsible for the altered functioning of the enteric nervous system and the central nervous system. There is evidence that the KP is sensitive to changes in the concentration of many vitamins and minerals that play a crucial role as coenzymes and cofactors in the de novo synthesis of nicotinamide adenine dinucleotide coenzyme. A reduction in the availability of the active form of vitamin B6 (pyridoxal 5'-phosphate, PLP) is known to affect tryptophan hydroxylase, kynurenine aminotransferase and kynureninase (KYNU). Vitamin B2 deficiencies result in a reduction in the activity of the flavin adenine dinucleotide dependent enzyme, kynurenine 3-monooxygenase. Minerals are also responsible for the proper functioning of enzymes engaged in L-tryptophan metabolism. Mn(2+), Zn(2+), Co(2+) and Cu(2+) influence KYNU activity, and Mg(2+) regulates quinolinate phosphoribosyl transferase. Fe(2+) is responsible for the proper functioning of both indoleamine 2,3-dioxygenase and 3-hydroxy-anthranilic acid dioxygenase. Changes in the concentration of KP metabolites and in enzymatic activity have been found in many pathological states. Therefore, it is justifiable to regulate the concentration of certain kynurenines or enzymes in the KP which may provide a potential therapeutic target for the treatment of various health impairments. This review demonstrates the role of vitamin and mineral activity on the KP, which may have an effect on the proper functioning of the human organism. Surplus administration of vitamins did not elicit any beneficial effects on L-tryptophan metabolism. Whether a mineral surplus influences L-tryptophan metabolism is still not established. It seems that cofactor deficiencies influence the KP far more than surpluses.

The influence of steroids on noradrenaline-mediated contractile reactivity of the superficial nasal and facial veins in cycling gilts.

The nasal venous blood may be directed through the facial vein into the systemic circulation or through the frontal vein into the venous cavernous sinus of the perihypophyseal vascular complex, where hormones and pheromones permeate from the venous blood into the arterial blood supplying the brain and hypophysis. The present study was designed to determine the effect of noradrenaline (NA) on the tension of the nasal, frontal and facial veins of cycling gilts, and influence of ovarian steroid hormones on NA-mediated contractile reactivity. Additionally, the enzyme dopamine-beta-hydroxylase catalysing the conversion of dopamine to noradrenaline (DbetaH) was immunolocalized in these vessels. Among three studied veins, the frontal proximal vein, that fulfill a key role in the supply of the nasal venous blood into the venous cavernous sinus, reacted to NA most strongly (P < 0.001) and this reaction was weaker in the periestrous period than in luteal phase (P < 0.001). Inversely, the reaction to NA of the facial proximal vein, that carry blood to the peripheral circulation, was stronger in the periestrous period than in luteal phase (P < 0.05). P4, E2 and T significantly lowered NA-mediated tension of the frontal proximal vein during the periestrous period (P < 0.001), while in the luteal phase P4 might antagonize relaxing effect of E2 to this vessel. The result suggests that supply of the nasal venous blood into the venous cavernous sinus is greater during the periestrous period than during the luteal phase. DbetaH was clearly expressed in the muscular layer of the isolated superficial nasal and facial veins of gilts in both studied stages of the estrous cycle. We suggest that the reactivity of the superficial veins of the nose and face to NA combined with the previously demonstrated reactivity of these veins to steroid ovarian hormones and male steroid pheromones may regulate the access of priming pheromone androstenol (resorebed in the nasal cavity) to the brain of gilts during periestrous period via humoral local destination transfer.

The effect of lateral electrical surface stimulation (LESS) on motor end-plates in an animal model of experimental scoliosis.

The treatment of idiopathic scoliosis is challenging because of its diverse etiology, age of onset, and long duration of intensive treatment. We examined the effect of lateral electrical surface stimulation (LESS) in an animal model of experimental scoliosis (ES) assessing the number of motor end-plates (MEPs) as a study end-point. The control group (n=5) was adapted to the experimental apparatus without stimulation, whereas ES was induced in rabbits by one-sided LESS of the longissimus dorsi muscle (LDM) for a duration of 2 months. The ES group (n=5) were subjected to a short-term corrective electrostimulation applied at the contralateral side of the spine compared to the previous LESS stimulation for 2 h daily for 3 (n=5) or 6 months (n=5). Another group of ES rabbits was subjected to a long-term corrective electrostimulation applied for 9 h daily for 3 (n=5) or 6 months (n=5). LESS applied for 2 months (ES), significantly increased the number of MEPs in LDM. The short-term corrective electrostimulation for 3 months resulted in an increased number of MEPs. However, a decrease was observed in the animals treated for 6 months. The long-term corrective electrostimulation for 3 months did not change the density of MEPs in the LDM, but for 6 months the number of MEPs in the LMD significantly decreased by ES and control groups. Thus, the results of the present study clearly show that the short-term LESS is able to influence both the number of MEPs and the effectiveness of muscle correctional adaptation in a more efficient and harmless manner than the long-term procedure.

Relationship between contractions of the uterus and concentration of PGF2α in uterine venous blood after luteolysis in gilts.

The origin and physiological significance of high pulses of prostaglandin F2α (PGF2α) in uterine venous blood that occur 2-3 days after luteolysis are not well understood. We studied the relationship between contractions of the uterus evoked by exogenous oxytocin (OT) and PGF2α concentration in uterine venous blood on day 17 of the porcine oestrous cycle. The infusion of OT into the uterine artery produced an immediate increase in the uterine intraluminal pressure (UIP) (p < 0.001) and a simultaneous elevation in PGF2α concentration in uterine venous blood (p < 0.0001). The infusion of indomethacin (IND) into the uterine artery slightly decreased PGF2α concentration in uterine venous blood, but it did not suppress uterine contraction or the rapid increase in PGF2α concentration in uterine venous blood just after OT infusion (p < 0.0001), which was lower that in gilts not treated with IND. We conclude that the spikes of PGF2α concentration in uterine venous blood occurring after OT infusion on day 17 of the porcine oestrous cycle are mainly caused by the excretion with venous blood from the remodelled uterus and that PGF2α synthesis may contribute to this. These results suggest that the high spikes in PGF2α concentration that occur 2-3 days after luteolysis in pigs, sheep, cows and mares all have a similar origin.

The influence of steroids on the vascular tension of isolated superficial nasal and facial veins in gilts during sexual maturation.

The arrangement of the superficial facial veins enables blood flow from the nasal cavity into the peripheral circulation by two pathways: through the facial vein into the external jugular vein and through the frontal vein into the cavernous sinus. The venous cavernous sinus is the site where hormones and pheromones permeate from venous blood into the arterial blood supplying the brain and hypophysis. The present study was designed to: (1) determine whether estradiol (E2) and progesterone (P4) affect the vascular tone of the superficial veins of the nose and face in maturating prepubertal gilts (PP) and in prepubertal gilts deprived of ovarian hormones (PPov), and (2) to analyze the immunolocalization of progesterone receptors (PR), and estradiol receptors alpha (ER alpha) and beta (ER beta) in these veins. The influence of hormones on the vascular tension differed depending on the type of vessel, the hormonal status and dose of hormone used. Estradiol decreased the vascular tension in the nasal and facial veins of PP gilts (P < 0.01). In PPov gilts, the effect of E2 was opposing, however it caused strong tension in the proximal and distal parts of the facial vein (P < 0.01 and P < 0.001, respectively). Progesterone increased the vascular tension in the proximal segment of the nasal vein and in the distal segment of the frontal and facial veins, and decreased the tension in the distal segment of the nasal and facial veins (P < 0.05) of PP gilts. In PPov gilts, P4 produced strong increase in the tension of distal and proximal segments of the nasal vein (P < 0.001 and P < 0.01, respectively) and of distal segment of the facial vein (P < 0.01), strong decrease in the tension of the distal part of the nasal vein (P < 0.01) and had limited effect on other veins. Expression of ER beta, but not of PR, was observed in the superficial nasal and facial veins. In conclusion, the ovarian steroid hormones that modulate the vascular tension of the nasal and facial veins in prepubertal gilts may influence the transfer of boar pheromones from the nasal mucosa to the brain via local humoral pathway during sexual maturation.

The influence of steroids on vascular tension of isolated superficial veins of the nose and face during the estrous cycle of gilts.

The arrangement of the superficial facial veins enables blood flow from the nasal cavity into the peripheral circulation by two pathways: through the frontal vein into the cavernous sinus and through the facial vein into the external jugular vein. The current study was designed to determine whether estradiol and progesterone affect the vascular tone of the superficial veins of the nose and face in cycling gilts (Sus scrofa f. domestica) and to analyze the immunolocalization of progesterone receptors and estradiol receptors in these veins. The influence of hormones on vascular tension differed depending on the type of vessel and the phase of the estrous cycle. Estradiol decreased vascular tension in the nasal vein during the follicular phase (P<0.05) and increased tension in the frontal vein during the luteal phase (P<0.05). Progesterone increased the vascular tension of the frontal vein (P<0.05) and decreased the tension of the other veins (P<0.05) in both phases of the cycle. Expression of estradiol receptor beta but not of progesterone receptor was observed in the superficial veins of the nose and face. In conclusion, the effect of ovarian steroid hormones on the vascular tension of the superficial veins of the nose and face in female pigs as well as the reactivity of these veins to steroid boar pheromones can affect the blood supply from the nasal cavity to the venous cavernous sinus. We propose that the ovarian steroid hormones that modulate the vascular tension of the nasal and facial veins may also influence the action of boar pheromones absorbed into the nasal mucosa in gilts and may reach the brain via local destination transfer.

Retrograde transfer of 125I-radiolabelled activin and inhibin in the periovarian vascular complex in the sow.

This study investigated whether activin A and an inhibin-alpha subunit fragment (INHalpha) could permeate in a periovarian vascular complex from ovarian effluent into the ovarian artery and be retrograde transferred into the ovary. Radiolabelled activin A (125I-activin A) and INHalpha (125I-INHalpha) were injected (2.7 x 10(7) dpm) into follicles or corpora lutea (CL). It was demonstrated that 125I-activin A and 125I-INHalpha were released into the ovarian effluent and permeated into the arterial blood supplying the ovary in both phases of the cycle. The concentration of 125I-activin A in ovarian arterial blood was higher in the luteal phase (LP) than in the follicular phase (FP) (P<0.0001) in contrast to 125I-INHalpha which was higher in the FP (P<0.0001). The concentration of 125I-activin A in uterine tissues generally did not differ between the phases of the estrous cycle, but the concentration of 125I-INHalpha was higher (P<0.05) in the FP than in the LP. The concentration of 125I-activin A was higher in the LP in samples of endometrium and myometrium (P<0.05), as well as mesometrium (P<0.01), and higher in the FP in samples of mesometrium (P<0.05) close to the ovary than in the samples adjoining the uterine body. In the FP, the concentration of 125I-INHalpha was higher in endometrium and mesometrium close to the ovary than in samples adjoining the uterine body (P<0.05). In conclusion, the study demonstrated that it was possible for INHalpha and activin A to be retrograde transferred to the ovary. Thus this transfer could elevate their concentration in arterial blood supplied to the ovarian follicles or CL and may influence production of these peptides in the ovary, modulating ovarian function.

The influence of boar pheromones on the contractile reactivity of the isolated superficial veins of the nose and face in ovariectomized prepubertal gilts and in gilts during sexual maturation.

This study was designed to establish: a) whether boar pheromones, 5alpha-androstenone and 5alpha-androstenol, may affect the contractile reactivity of superficial veins of the face in prepubertal gilts deprived of ovarian hormones, and b) what is the influence of ovarian hormones secreted during sexual maturation on the contractility of these veins. The isolated rings of frontal, facial and dorsal nasal veins were treated with androstenone (5alpha-androst-16-en-3-one), androstenol (5alpha-androst-16-en-3-ol) and testosterone (17beta-hydroxy-4-androsten-3-one) in concentrations of either 1 or 10 microM. Changes in the contractile activity of the isolated vein segments were measured using isometric transducer and recorded on HSE-ACAD W software. Sex boar pheromones androstenol and androstenone affected the contractility of the superficial veins of the face and nose in both of the prepubertal ovariectomized gilts and prepubertal intact animals. The way these veins reacted to pheromones differed between animal groups, particular vessels and even their parts and was also dose - dependent. In prepubertal ovariectomized gilts, androstenol had stronger action and caused the constriction of the facial vein, dorsal nasal vein and the distal part of the frontal vein. Androstenone produced constriction of the nasal vein, distal part of the frontal vein and proximal part of facial vein, but relaxation of the proximal part of the frontal vein and the distal part of the facial vein. In prepubertal untreated gilts, androstenone was more effective and strongly influence on the constricted of the frontal vein and facial vein and produced the relaxation of the nasal vein. Androstenol influence on the constriction the frontal vein and the distal parts of the facial vein and nasal vein, and influence o the relaxtion their proximal parts. Testosterone used as a control androgen affected both superficial veins of the face veins in a dose-dependent manner, and, at a higher dose, increased the contractility more effectively. Only the nasal vein did not react to this hormone. The present results suggest the existence in prepubertal gilts of frontal and facial veins' specific reactivity which may participate in the regulation of blood flow from the nasal cavity to the perihypophyseal vascular complex and play a role in the humoral pathway for the male pheromone priming functions in the central nervous system. This reactivity was displayed by the vessels in prepubertal gilts without ovarian hormones. The presence of active ovaries in maturing gilts changed the reactivity of these veins to pheromones and testosterone.

The influence of boar pheromones on the vasoreactivity of the facial superficial veins in ovariectomized and estradiol-treated pubertal gilts.

This study was designed to establish: a) whether boar pheromones, androstenone and androstenol, may affect the vasocontractility of the facial superficial veins in ovariectomized pubertal gilts and b) what is the effect of estradiol on this contractility. The gilts ovariectomized after two controlled estrous cycles, and the ovariectomized gilts treated with estradiol benzoate were used in the experiment. The isolated rings of dorsal nasal, frontal and facial veins were incubated with androstenone (5alpha-androst-16-en-3-one) and androstenol (5alpha-androst-16-en-3-ol) in concentrations of either 1 or 10 microM. Changes in the contractile activity of the isolated vein segments were measured using isometric transducer and recorded with HSE-ACAD W software. In ovariectomized gilts both the androstenone and androstenol caused a relaxing effect on the nasal vein, flow of the blood from the nasal cavity, and on the frontal vein, by which the blood may by directed into the perihypophyseal vascular complex. An opposing reaction to these pheromones was found in the distal part of the facial vein by which the blood is directed to the systemic circulation. Treating ovariectomized gilts with estradiol benzoate changed mainly the reactivity of the frontal vein to androstenone, which produces constriction, but this treatment did not affect the reactivity of the facial superficial veins to androstenol. The present results demonstrated that both boar sex pheromones, androstenone and androstenol, may contribute to the regulation of their humoral pathway from the nasal cavity to the brain and hypophysis in the ovariectomized pubertal gilts and suggest the effect of estradiol to this pathway.

The influence of male pheromones on the contractile reactivity of the isolated superficial veins of the nose and face during the estrous cycle in gilts.

This study was designed to determine whether steroid sex pheromones of the boar may affect the contractile activity of the superficial venous vessels of the nose and face in gilts, and in this way contribute to recently discovered humoral transfer of pheromones to the brain and hypophysis. The dependence between the reactivity of nasal and facial veins to male pheromones and the phase of the estrous cycle in gilts was also studied. The gilts were used in the luteal phase of the cycle and in the follicular phase of the cycle. The dorsal nasal, frontal and facial veins were isolated on an appropriate day of the estrous cycle. The isolated rings of veins were treated with androstenone (5alpha-androst-16-en-3-one), androstenol (5alpha-androst-16-en-3-ol) and testosterone (17beta-hydroxy-4-androsten-3-one) in concentrations of 1 or 10 microM. Changes in the contractile activity of the isolated vein segments were measured using isometric transducer and recorded on HSE-ACAD software for Windows. Androstenone--main signaling boar pheromone--induced much stronger reactions of the vessels than androstenol. Androstenone caused significant relaxation of the dorsal nasal and frontal veins, and significant increased tension of the facial vein in the follicular phase of the estrous cycle. The results obtained suggest a direct effect of male pheromones on the contractile reactivity of the superficial veins of the nose and face in the female, and in this way contribute to a humoral pathway for transfer of pheromones to the brain and hypophysis. Moreover, the present study revealed changes in the reactivity during the estrous cycle of the veins, transporting blood from the region of the nasal cavity, to male pheromones participating in the regulation of female reproductive processes.

Retrograde transfer of steroid hormones to the ovary in luteal and follicular phases of porcine oestrous cycle in vivo.

The efficiency of the retrograde transfer of steroid ovarian hormones from the ovarian effluent into blood supplying the ovary and the rate of its back transport to the ovary were determined for the first time in in vivo conditions. Sexually mature gilts (n = 25) were used in the physiological study. The concentration of oestradiol and progesterone in blood collected from the ovarian artery was higher in both the follicular phase (by 87.9 +/- 2.9% and 150.0 +/- 4.8%, respectively, P < 0.001) and the luteal phase (by 82.1 +/- 3.9% and 77.7 +/- 2.7%, respectively, P < 0.001) than in systemic blood reaching the initial part of the ovarian artery. The high efficiency of the retrograde transfer was not dependent on the concentration of hormones in the ovarian venous blood. However, the efficiency and rate of the retrograde transfer differed between phases of the oestrous cycle. We suggest that such effective retrograde transfer of ovarian hormones must affect the secretory function of the ovary.

The concentrations of catecholamines and oxytocin receptors in the oviduct and its contractile activity in cows during the estrous cycle.

UNLABELLED: In vitro experiments on oviducts of cyclic cows were undertaken to study: (1) the content of dopamine (DA), noradrenaline (NA) and adrenaline (A) in infundibulum, ampulla and isthmus, (2) the concentration of oxytocin receptors (OTR) in oviductal tissues and (3) the motility of ampulla and isthmus. Changes of DA content were observed in the infundibulum and the ampulla with maximal values occurring on Days 6-10 of the estrous cycle. The mean NA content was greatest in infundibulum

Apoptotic cell death in the porcine endometrium during the oestrous cycle.

It has been reported that apoptosis plays an essential role in controlling the physiological cell kinetics in the human and rodent endometrium but this type of death has never been studied in the porcine endometrium. The aim of this study was to investigate the apoptotic cell death in the porcine endometrium during the middle (Days 9-11) and late (Day 13) luteal phase, during the luteolysis (Day 15) and early follicular phase (Days 17-19) of the oestrous cycle. Apoptotic cells were identified by in situ DNA 3'-end labelling method. It was revealed that the greatest number of apoptotic cells in the luminal and glandular epithelium was found on Days 17-19 and on Day 15 of the oestrous cycle, respectively. In the stroma, the greatest number of these cells was found on Days 9-11. Our data have shown that in the porcine endometrium, both epithelial and stromal cells undergo apoptosis and that the number of apoptotic cells varies depending on the phase of the oestrous cycle.

Morphology of the dorsal nasal, frontal and facial veins in adult gilts.

Morphological examinations conducted on adult gilts indicate that the dorsal nasal, frontal and facial veins belong to the myoelastic type with a well-developed internal elastic lamina and a thick tunica media with elastic fibers. Smooth muscle cells in the tunica media are mainly arranged circularly. A characteristic feature of individual veins, and even their parts, was the difference in the distribution and number of elastic fibers and amount of collagen, both in the internal elastic lamina and tunica media. Slight thickening of the vessel walls and a decrease in the number of elastic fibers were observed in the distal part of the dorsal nasal vein and in the proximal parts of the frontal and facial veins. No valves were found in the frontal vein. The bundles of smooth muscle cells in the tunica media and elastic fibers surrounding them were rounded, not laminar like in the other veins. Characteristic, sandwich-like arranged smooth muscle bundles, elastic fibers and large amounts of collagen were observed in the tunica media of the distal part of the facial vein. A distinctive feature of the middle auricular and radial veins was the presence of a well-visible external elastic lamina in the adventitia. An evaluation of the luminous vein surface in a SEM shows that endothelial cells are elongated and arranged consistently with the direction of blood flow in almost all of the veins analyzed. Endothelial cells were less elongated in the distal part of the facial vein, and microvilli were present on them.

Humoral pathway for local transfer of the priming pheromone androstenol from the nasal cavity to the brain and hypophysis in anaesthetized gilts.

It is generally accepted that pheromones act by stimulating of the dendritic receptors of the olfactory neurones massed in the olfactory epithelium. This study was designed to ascertain whether it is possible for the boar pheromone androstenol (5alpha-androst-16-en-3-ol) to be transported from the nasal cavity of anaesthetized gilts to the brain and hypophysis via local transfer from the blood in the perihypophyseal vascular complex. The experiment was performed on days 18-21 of the porcine oestrous cycle (crossbred gilts, n = 6). Tritiated androstenol (3H-A; total amount 10(8) d.p.m. (758 ng)) was applied for 1 min onto the respiratory part of the nasal mucosa, 4-6 cm from the opening of the nares. Arterial blood samples from the aorta and from the carotid rete were collected every 2 min during the 60 min period following administration of the steroid. Total radioactive venous effluent from the head was removed and an adequate volume of homologous blood was transfused into the heart through the carotid external vein. At the end of the experiment gilts were killed and tissue samples of the hypophysis and some brain structures were collected to measure radioactivity. In addition, corresponding control tissues were collected from three untreated gilts and from three heads of gilts 60 min after 3H-A was applied post mortem into the nasal cavity. The concentration of 3H-A was significantly higher (P < 0.0001) in the arterial blood of the carotid rete than that of aorta. The mean rate of 3H-A counter current transfer from venous to arterial blood in the perihypophyseal vascular complex, expressed as the ratio of the 3H-A concentration in arterial blood of the carotid rete to the 3H-A concentration in blood sampled simultaneously from the aorta, was 1.96 +/- 0.1. The concentration of 3H-A in plasma from the venous effluent from the head ranged from 1.3 to 1.8 pg x ml(-1). During the 60 min period of the experiment, 0.68% of the total applied dose of 3H-A was resorbed from the nasal cavity into the venous blood. Moreover, we found that 3H-A was present in the olfactory bulb (P <0.01), amygdala, septum, hypothalamus, adenohypophysis, neurohypophysis (P > 0.05) and perihypophyseal vascular complex (P < 0.01). These results demonstrate that, in anaesthetized gilts, the boar pheromone androstenol may be resorbed from the nasal mucosa, transferred in the perihypophyseal vascular complex into arterial blood supplying the brain and hypophysis, and then arrested in the hypophysis and certain brain structures. We suggest that in addition to the standard neural pathway for signalling pheromones, another pathway exists whereby androstenol, as a priming pheromone, may be resorbed from the nasal cavity into the bloodstream and then pass locally from the perihypophyseal vascular complex into the arterial blood supplying the brain and hypophysis, thus avoiding the first passage metabolism in the liver.

Humoral pathway for transfer of the boar pheromone, androstenol, from the nasal mucosa to the brain and hypophysis of gilts.

Signaling and priming pheromones play an important role in intraspecies behavioral and sexual interactions and in the control of reproduction. It is generally accepted that pheromones act by stimulating the dendritic receptors in the mucus-imbedded cilia of olfactory neurons massed in the olfactory epithelium. The boar pheromone androstenol, known to induce sexual behavior in pigs, is 1 of 2 pheromones that have been chemically defined, tritiated and thus made available for use in studies. In Experiment 1, sexually mature cyclic gilts at Days 16 to 21 of the estrous cycle were humanely killed and the heads separated from the bodies. The heads were attached to a perfusion system using heated, oxygenated, heparinized, autologous blood. A total amount of 10(8) dpm (758 ng) of 3H-5 alpha-androstenol (3HA) was either infused into the angularis oculi veins that drain the nasal cavities (n = 7) over a 5-min period or applied through intranasal catheters onto the mucose surface (n = 16) for 2 min. In both groups frequent blood samples were collected from the carotid rete and from venous effluent. Concentration of 3HA in the arterial blood of the carotid rete after direct (into angularis oculi veins) or indirect (onto the nasal mucosa) administration of 3HA into veins draining the nasal cavities was significantly higher than background radioactivity before 3HA administration (P < 0.0001 and P < 0.05, respectively). The 3HA was selectively accumulated (compared with the respective control tissue) in the neurohypophysis (P < 0.001), adenohypophysis (P < 0.01), ventromedial hypothalamus (P < 0.05), corpus mammillare (P < 0.01), and perihypophyseal vascular complex (P < 0.001). In a second in vitro experiment, active uptake of 3HA into the nasal mucosa of the proximal, respiratory segment of the nasal cavity was observed. These results demonstrate a humoral pathway for the transfer of pheromones from the nasal cavity to the hypophysis and brain. Androstenol was taken up by the respiratory part of the nasal mucosa, resorbed into blood, transported to the cavernous sinus and transferred into the arterial blood of the carotid rete (supplying the hypophysis and brain), and then selectively accumulated in the hypophysis and certain brain structures.

The inhibitory effect of hCG on counter current transfer of GnRH and the presence of LH/hCG receptors in the perihypophyseal cavernous sinus--carotid rete vascular complex of ewes.

The existence of the hormone passage from venous blood into arterial blood in the area of the perihypophyseal vascular complex has been demonstrated in some mammals, but its mechanism has not been defined. To study the regulatory mechanism we infused hCG into perihypophyseal cavernous sinus of ovariectomized, conscious ewes to test if the hCG would affect putative LH/hCG receptors and inhibit counter-current transfer of GnRH from the venous cavernous sinus to the arterial carotid rete. The latter study was done on an isolated head model. Ewes were ovariectomized in mid-anestrus and, after 4 to 5 wk were used in the experiments. On the day of experiment ewes were treated intramuscularly with estradiol benzoate or oil vehicle, and 18 to 20 h later were infused either with a multielectrolyte solution or hCG for 2 h via the venae angularis oculi. Immediately thereafter the ewes were anesthetized and exanguinated, and subsequently decapitated. The isolated head was perfused with Dextran in multielectrolyte. The 125I-GnRH was infused into the cavernous sinus via the venae angularis oculi for 5 min; contemporaneous samples were taken from the carotid rete and both jugular veins at 1-min intervals. Transfer of 125I-GnRH from the cavernous sinus to the carotid rete was inhibited by hCG in ewes pretreated with estradiol benzoate but not with oil (P<0.005). We collected tissue samples from the vascular complex of the cavernous sinus and carotid rete of cyclic ewes to determine the presence of LH/hCG receptors. In situ hybridization showed the presence of LH/hCG receptor mRNA transcripts in the walls of both arterial and venous compartments of the cavernous sinus-carotid rete complex, and immunohistochemistry revealed the presence of receptor proteins. These novel findings confirm previously obtained data suggesting that LH is a modulatory factor for the counter-current transfer of neuropeptides from the venous blood of the cavernous sinus to the arterial blood supplying the brain and hypophysis. The LH could modulate 125I-GnRH transfer acting directly on the vascular smooth muscle.

Local increase of ovarian steroid hormone concentration in blood supplying the oviduct and uterus during early pregnancy of sows.

Countercurrent transfer in the ovarian vascular pedicle elevates the concentration of steroid hormones in blood supplying the oviduct and periovarian part of the uterus during the estrous cycle in the pig. This study was conducted to determine whether during early pregnancy the arterial blood supply to the oviduct and uterus carries greater concentration of steroid hormone than systemic blood. The concentration of ovarian steroid hormones (progesterone, estradiol-17 beta, estrone, androstenedione and testosterone) was measured in 40 gilts on Days 12, 18, 25 or 35 of pregnancy. Silastic catheters were inserted: a) into the jugular vein, b) into the branch of uterine artery close to the ovary (proximal to the ovary) and c) into the branch of the uterine artery close to the cervix (distal to the ovary). On the day following surgery simultaneous blood samples from cannulated vessels were collected every 20 min for 3 hours. The concentration of steroid hormones was determined by radioimmunoassay. The mean concentrations of studied hormones in branches of the uterine artery proximal and distal to the ovary were significantly greater than in the jugular vein (P < 0.001) by 18 to 69% and 7 to 31%, respectively. The concentrations of hormones in proximal and distal to the ovary branch of the uterine artery were also significantly different (P < 0.001). The increase in concentrations of the measured hormones did not differ considerably between investigated days of pregnancy. It is concluded that during maternal recognition of pregnancy, formation of the corpus luteum of pregnancy, implantation of the embryo and the placenta elongation the oviduct and uterus are supplied with locally elevated concentration of steroid hormones compared to systemic blood.

Countercurrent transfer of 125I-LHRH in the perihypophyseal cavernous sinus-carotid rete vascular complex, demonstrated on isolated pig heads perfused with autologous blood.

The objective of the study was to determine whether the local permeability of luteinizing hormone-releasing hormone (LHRH) from the venous blood of the perihypophyseal cavernous sinus into the arterial blood of the carotid rete, supplying the brain and hypophysis in gilts, depends on the day of the estrous cycle, as well as to determine whether this transfer exists when LH concentration in the blood is reduced (the experimental short-loop negative feedback for LH secretion after estradiol injection in ovariectomized gilts). Experiments were conducted on isolated gilt heads with necks, on chosen days of the estrous cycle (n = 40), and on previously ovariectomized gilts treated with estradiol benzoate (EB) (n = 5) or corn oil (n = 3). After exsanguination, the gilt heads with necks were disarticulated and about 30-45 min later were supplied with autologous, oxygenated, and heated blood at a stable blood flow and pressure through the left carotid artery for 30 min. 125I-LHRH was infused into both cavernous sinuses through the cannulated angularis oculi veins for 5 min. After 125I-LHRH infusion, radiolabeled LHRH was found (P < 0.001) in arterial blood taken from the carotid rete through the open right carotid artery in all animals used in the experiment: on Days 1-2 (six gilts), on Days 12-14 (seven gilts) of the estrous cycle, and in five ovariectomized gilts during negative feedback for LH surge (40 hr after EB). No significant radioactivity of 125I-LHRH was found in the arterial blood on Days 3-5 (n = 6), 9-11 (n = 4), and 15-21 (n = 17) of the estrous cycle. A very low level of radioactivity was found in the ovariectomized control group after the injection of corn oil (n = 3). These results provide evidence for the permeability of LHRH from the venous to the arterial blood and its retrograde transport with the arterial blood to the hypophysis and brain, after the ovulation period (Days 1-2) and on Days 12-14 of the estrous cycle. This suggests that a close relationship exists between the day of the estrous cycle and LHRH permeability from the venous to the arterial blood in the perihypophyseal cavernous sinus-the carotid rete complex in gilts-and that this mechanism may be included in a short-loop feedback for LHRH secretion.

Involvement of adrenoceptors in the ovarian vascular pedicle in the regulation of counter current transfer of steroid hormones to the arterial blood supplying the oviduct and uterus of pigs.

1. On Day 10 of the oestrous cycle in pigs, after laparotomy noradrenaline (NA), methoxamine (alpha 1-adrenomimetic, M), Prazosin (alpha 1-adrenolytic, Pr) in total doses of 4 mumol, and saline were infused (10 min) into the superficial layer of mesovarium on both sides of the ovarian pedicle vasculature, close to the ovary. 2. Blood flow in the ovarian artery, heart rate and progesterone (P4) and androstenedione (A4) secretion from the ovary and their concentrations in the ovarian venous effluent, as well as the concentrations of P4 and A4 in the blood supplying the oviduct and the uterus, were determined. 3. A significant increase of P4 and A4 secretion after NA and M infusion and increased concentrations of P4 and A4 in the ovarian venous effluent were found, but these changes did not influence the counter current transfer of hormones from the venous effluent into arterial blood supplying the oviduct and the uterus. 4. Infusion of Pr caused a significant decrease of P4 and A4 secretion and their concentrations in the ovarian venous effluent and significantly increased A4 concentration in the blood supplying the oviduct and uterus. 5. The results indicate that stimulation of alpha 1-adrenoceptors in the area of ovarian vasculature did not influence, whereas block of alpha 1-adrenoceptors affected, the local concentration of steroid hormones in the blood supplying the oviduct and the part of the uterus proximal to the ovary, despite the changes in the concentrations of steroid hormones in the ovarian effluent.