Effects of neonatal and prepubertal hormonal manipulations upon estrogen neuroprotection of the nigrostriatal dopaminergic system within female and male mice.

Estrogen (E) can function as a neuroprotectant of the nigrostriatal dopaminergic (NSDA) system against methamphetamine (MA) neurotoxicity in female, but not male, mice. In the present report we examined whether the organizational effects of gonadal steroid hormones, as exerted in the early postnatal period, or developmental effects, as exerted during the pubertal period, would contribute to this sexually dimorphic neuroprotectant action of E. Neonatal gonadectomy and treatment with testosterone of female mice, retained the ability to show an E neuroprotectant response when tested as adults. However, females not treated with gonadal steroids failed to show an E-dependent neuroprotectant response. Neonatal gonadectomy of male mice, failed to result in the display of an E neuroprotectant response when tested as adults. Prepubertal gonadectomy of female mice, with or without testosterone treatment, abolished the capacity for E to produce neuroprotection against MA-induced NSDA neurotoxicity. Nor did prepubertal gonadectomy enable male mice to show an E neuroprotectant response. Taken together these results demonstrate that none of the manipulations performed within male mice enabled them to show an E-dependent neuroprotective response against MA-induced neurotoxicity of the NSDA system when tested as adults. For the female, it appears that the presences of gonadal steroids at these two developmental periods are needed for the display of an E-dependent neuroprotectant response within the adult.

Estrogen modulates responses of striatal dopamine neurons to MPP(+): evaluations using in vitro and in vivo techniques.

In vitro superfusion and in vivo electrochemistry were used to investigate the role of estrogen in modulating MPP(+)-induced dopamine output in the corpus striatum and nucleus accumbens of ovariectomized female rats. For in vitro superfusion experiments, dopamine and dihydroxyphenylacetic acid release were determined using HPLC with electrochemical detection from superfusion of corpus striatum fragments with Kreb's ringer phosphate buffer pulsed with MPP(+) alone or MPP(+) with estrogen. The in vivo electrochemistry experiments recorded the dopamine signal from carbon fiber microelectrodes stereotaxically passed through the corpus striatum and nucleus accumbens. Dopamine release was stimulated by pressure ejection of MPP(+) alone or in combination with estrogen through glass micropipettes fastened to the electrodes. Dopamine output from superfusion chambers which received infusion of MPP(+) with estrogen showed significantly lower output of dopamine compared with chambers which received MPP(+) alone. Outputs of dihydroxyphenylacetic acid did not increase following MPP(+) infusions. Data from the electrochemistry experiments demonstrated that estrogen significantly reduced both the amplitude and clearance rates of the MPP(+)-evoked dopamine signal in both the corpus striatum and nucleus accumbens. Results of this study demonstrate that: (1) MPP(+) evokes striatal dopamine release and this effect is significantly reduced in the presence of estrogen as determined by both in vivo electrochemistry and in vitro superfusion: (2) similar, albeit attenuated effects are observed in the nucleus accumbens as determined with in vivo electrochemistry; (3) estrogen acts to inhibit the clearance of dopamine in both the striatum and nucleus accumbens; and (4) estrogen may function as a neuroprotectant by reducing the uptake of neurotoxin into dopaminergic neurons.

The effects of castration on relaxation of rat corpus cavernosum smooth muscle in vitro.

PURPOSE: This study was conducted to investigate the role of testosterone (T) in regulating the relaxation of isolated rat corpus cavernosum strips in vitro. MATERIALS AND METHODS: Male rats were divided into treatment groups of intact, castrate, and castrate with T replacement. Norepinephrine (NE) was added to contract each of the tissue strips. Next, sodium nitroprusside (SNP), experiment I, or 8-Br-cGMP, experiment II, was added to relax the cavernosum tissue. Percent relaxations were recorded for each treatment group at each dose level. RESULTS: SNP was added to the NE-contracted tissues in doses of 10(-4) and 10(-3) M. In this experiment, castration significantly reduced tissue responsiveness to SNP and T replacement restored the response to intact levels. In the second experiment 8-Br-cGMP was added to the NE-contracted tissues in doses of 10(-5) and 10(-4) M. 8-Br-cGMP 10(-4) M was significantly less effective in relaxing tissue from castrate animals as compared with intact controls. Again, T treatment restored the response to intact levels. CONCLUSIONS: Our results show a clear role of T in regulating the ability of corpus cavernosum tissue to relax when treated with SNP or 8-Br-cGMP in vitro. In addition, the data suggests that T regulates sites distal to the formation of cGMP in the relaxation pathway.

Relative androgen sensitivity of the vascular and striated-muscle systems regulating penile erection in rats.

In this study we sought to compare the androgen sensitivity of the penile vascular erectile system with that of the striated muscles that augment the vascular effectors. All males were castrated 2 weeks before the experiments. At the time of castration, all males were implanted SC with a 45-mm testosterone (T)-filled Silastic capsule to maintain reflexive erections in ex copula tests. Experimental males had the bulbospongiosus (bulbocavernosus and levator ani) and ischiocavernosus muscles removed, while control animals underwent sham muscle excision surgery. After two baseline penile reflex tests, the T capsules were removed, and the groups were compared for the rate of loss of penile responses over 5 weeks. After these tests were completed, the T capsules were reimplanted and the two groups were compared for the rate of restoration of penile reflexes. These tests were conducted at 6, 12, 24, 36, 48, 72, and 96 h after reimplantation of the T capsules. Our results demonstrated that the vascular effector mechanisms responsible for initiating erections are androgen sensitive. The effects of T withdrawal and replacement on erection latency and low intensity erections (E1s) were manifested at about the same rate in the vascular and striated muscle effector systems. In contrast, the restoration of moderate intensity erections (E2s) by T occurred at a faster rate in rats with intact penile muscles. This result suggests that T was acting on the striated muscle effector systems to augment penile erection during this time, presumably due to the bulbospongiosus muscle exerting greater force on the penile bulb.

Electromyographic analysis of male rat perineal muscles during copulation and reflexive erections.

Anatomical examination of the ventral bulbospongiosus (BS) muscle suggested that its proximal and distal portions may act during penile erection as a two-stage pump governing the intensity of glans erections. The coordination between these portions of the BS, and of the proximal BS with the ischiocavernosus (IC) muscle, was studied using electromyographic (EMG) recordings taken during copulation and reflexive erections. Mounts without intromission were accompanied by either strong IC activity with little or no proximal BS activity, or strong proximal BS activity preceding the onset of IC activity. Activity in the proximal BS during mounts was variable in both duration and amplitude but uniform in frequency. During mounts with intromission, EMG activity of the proximal BS consisted of two characteristic phases, an early phase of low-amplitude activity which was similar to proximal BS activity during nonintromissive mounts, followed by an intromissive phase of high-amplitude, high-frequency activity. During intromission patterns, IC activity reliably preceded proximal BS activity. Ejaculations were accompanied by stronger proximal BS activity than were other copulatory events and were followed by a series of proximal BS and IC bursts lasting for 10-20 seconds. During reflexive erections, EMG activity in the proximal BS was always fusiform and varied with the intensity of erection only in frequency. In contrast to the proximal BS, activity in the distal BS was similar in frequency and amplitude across copulatory and reflexive events. These findings suggest that: a) different motoneuron pools serve the different portions of the BS muscle; b) the distal BS does not differentially affect glans erection but may serve primarily to promote rigidity of the portion of the bulb that it surrounds, while the proximal BS acts as the variable aspect of a hypothetical two-stage pump, and c) activity in the IC must precede activity in the proximal BS to achieve intromission.

Rapid effect of testosterone on striated muscle activity in rats.

We addressed the question of how rapidly gonadal steroids might affect behavior by studying how fast testosterone (T) could augment the actions of the striated penile muscles and their associated penile reflexes. Eight male rats, functionally castrated 4 months before this study, bore chronically implanted electrodes in the bulbospongiosus (bulbocavernosus) muscle. The males were observed for the display of penile reflexes immediately after the injection of T (250 micrograms i.m.) and T propionate (250 micrograms s.c.), as well as after injections of only the oil vehicle. Overt penile responses were rare. However, in several tests subcutaneous twitching was observable near the midline posterior to the penis. These twitches were accompanied by electromyographic bursts and were attributed to contractions of the bulbospongiosus muscle. T reliably (p less than 0.025) accelerated the onset of electromyographic activity: 6 of the 8 males had electromyographic bursts before the 30-min limit, and 3 males responded within 6 min. This is the first demonstration of such a rapid action of androgens on behavior or its basis in striated muscle activity. The rapid muscular response to T was ascribed to steroid-sensitive neuronal membrane receptors. Such responsiveness could increase the intensity of penile reflexes within minutes after surges of luteinizing hormone and T have been induced by cues associated with estrous females and thereby could contribute to the fertility of mating.

Inhibition of sexual reflexes by lumbosacral injection of a GABAB agonist in the male rat.

The effects of gamma-aminobutyric acid (GABA) agonists on penile reflexes were investigated. An intrathecal injection of baclofen (0.2, 0.4, or 0.8 microgram), a GABAB receptor agonist, into the subarachnoid space of the lumbosacral spinal cord (L5-S1), resulted in a dose-related decrease in the number of animals responding in a penile reflex test. Doses of 0.2 and 0.4 microgram of baclofen decreased the number of erections; 0.4 microgram also increased the latency to the first glans erection. The highest dose of baclofen (0.8 microgram) completely inhibited penile responses in these tests. None of these doses, however, prevented rats from copulating to ejaculation. Antecedent ejaculation, which facilitated the onset of penile reflexes in saline controls, also blocked the inhibitory effects on penile responses by the lower doses (0.2 and 0.4 microgram) of baclofen, but was ineffective in animals treated with 0.8 microgram baclofen. In contrast to the inhibitory effects of baclofen in the lumbosacral cord, an intrathecal injection of baclofen (0.8 microgram) at thoracic segments (T8-T10) did not affect penile erections elicited following an ejaculation. The role of spinal GABAA receptors in sexual reflexes was assessed by intrathecal injection of a GABAA agonist. THIP (0.5.1. or 2 micrograms), onto the lumbosacral cord. Only at the largest dose of THIP were slight inhibitory effects on penile reflexes observed. Together, these data indicate that stimulation of GABAB receptors in the lumbosacral spinal cord inhibits erectile mechanisms ex copula.

GABAergic regulation of penile reflexes and copulation in rats.

In three experiments we investigated the role of the GABAergic system in regulating penile reflexes and copulation in rats. All males had the suspensory ligament of the penis removed 3 weeks before the experiments, thereby permitting the novel observation of penile body erections in addition to penile glans responses. In Experiments 1 and 2, rats were assigned to one of the following treatment groups: control (saline-injected); baclofen, a GABA-B receptor agonist (1 or 2 mg/kg); THIP, a GABA-A receptor agonist (5 mg/kg); or (+)bicuculline, a GABA-A receptor antagonist (0.25 mg/kg). Penile reflex tests began 20 min after SC injection. Baclofen treatment decreased the number of males responding with glans erections within the 30 min latency limit, and significantly reduced the number of glans erections displayed, in a dose-dependent manner. These results indicate that activation of GABA-B receptors inhibits penile reflexes outside the context of copulation (ex copula). Rats treated with baclofen also had a dose-dependent reduction in the ratio of clusters of glans erections to penile body erections, and a significant increase in the number of penile body erections observed prior to the first glans erection. These findings suggest that baclofen inhibited the mechanisms mediating penile glans responses more than those mediating penile body erections. Bicuculline was without effect in both experiments; THIP significantly increased erections in Experiment 2 but had no reliable effect in Experiment 1. Because baclofen inhibited penile responses in ex copula tests, Experiment 3 was designed to assess the effects of the same dosages of this agent on male copulatory behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian steroid regulation of basal pulsatile luteinizing hormone release between the mornings of proestrus and estrus in the rat.

The aim of this study was to examine the regulation of basal pulsatile LH release by ovarian estradiol (E2) and progesterone (P) during the interval between the mornings of proestrus and estrus in the rat estrous cycle. Pulsatile LH release was studied in six groups of rats bled continuously through jugular venous cannulae between 0930-1230 h at a rate of 50 microliter whole blood/5 min: 1) bled on proestrus; 2) sham ovariectomy (OVX) at 0900-1000 h on proestrus and bled on estrus; 3-6) OVX at 0900-1000 h on proestrus, implanted with either empty or E2-, P-, or E2- plus P-containing Silastic capsules, and bled 24 h after OVX. In our colony, plasma E2 levels peaked at 1300 h, remained high through 1730 h, and then declined. Plasma P values increased between 1300 and 1730 h, peaked at 2000 h, and were rapidly declining by 2400 h. To reproduce the magnitude as well as the temporal pattern for these changes in plasma E2 and P levels, E2 capsules were inserted at the time of OVX on proestrus and removed at 1830 h. P capsules were inserted at 1400 h and removed at 2300 h. Groups of ovariectomized or sham-ovariectomized control animals had empty capsules implanted and removed at comparable times. Capsules producing basal E2 and P levels were not inserted after the removal of the original implant, since mean blood LH levels, pulse amplitude, and frequency were the same in rats sham ovariectomized or ovariectomized at 1830 h on proestrus and bled the next morning between 0930-1230 h. Mean blood LH levels decreased between the mornings of proestrus and estrus due to a reduction in LH pulse frequency as pulse amplitude remained stable. OVX at 0900-1000 h on proestrus increased mean blood LH levels 2.5-fold compared to values on estrus due to increases in both LH pulse frequency and amplitude. Restoration of physiological proestrous levels of only E2 returned LH pulse frequency to estrous values, but did not significantly affect LH pulse amplitude. P alone also had no significant effect on LH pulse amplitude, but slightly reduced pulse frequency, although, unlike E2, not to values seen on estrus. Replacing both E2 and P returned LH pulse amplitude to estrous levels and reduced LH pulse frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of estradiol and progesterone on pulsatile LH secretion in 8-day ovariectomized rats.

Previous studies in our laboratory [Endocrinology 114: 1605-1612 (1984); Neuroendocrinology 41: 252-257 (1985)] examined the influence of ovarian steroids on pulsatile luteinizing hormone (LH) release, and involved immediate replacement following ovariectomy (OVX) of estradiol (E2) and progesterone (P) for a 24-hour period within the physiological context of the estrous cycle. The present study investigated the effects of replacing E2 and/or P 1 week after OVX, and therefore examined whether the time elapsed following OVX influences the effects of ovarian steroids on pulsatile LH release. Immediately after jugular venous cannulation, rats were implanted with either empty silastic capsules or capsules capable of restoring physiological levels of E2 and/or P comparable to those found in intact rats between the intervals of diestrus 1 (D1) and diestrus 2 (D2), or D2 and proestrous morning. 24 h later, these rats were bled continuously at a rate of 50 microliters whole blood/6 min for 3 h for analysis of pulsatile LH secretion. Rats with empty capsules had decreased levels of E2 and P and elevated mean blood LH levels, pulse amplitudes and frequencies. Two groups of animals with E2 capsules had plasma E2 levels comparable to those seen either in the D1-D2 or D2-proestrous intervals, decreased levels of P, and in both cases significant decreases in LH pulse amplitude, but no change in LH pulse frequency or basal LH secretion. Since mean blood LH levels in 8-day ovariectomized rats are determined by LH pulse amplitude, frequency and basal LH secretion [Neuroendocrinology 37: 421-426 (1983)].(ABSTRACT TRUNCATED AT 250 WORDS)

Anisomycin does not disrupt the activation of penile reflexes by testosterone in rats.

A possible role of protein synthetic processes in the testosterone-activation of penile reflexes in rats was examined in these experiments. In Experiment 1, long-term castrated male rats were injected with 250 micrograms testosterone propionate (TP) and tested for penile reflexes 24 hr later. Fifteen minutes prior to TP these males received a systemic injection of the protein synthesis inhibitor anisomycin (ANI) or the saline vehicle. ANI had no disruptive effect on the activation of penile reflexes by TP; in fact, ANI facilitated erection frequency. In Experiments 2 and 3, a series of three ANI or saline injections were given at 2 hr intervals beginning with the injection of 250 micrograms TP, with no significant effect on any reflex parameters tested 12 or 24 hr after TP. In Experiment 4, the penile reflexes of male rats were stimulated by implanting a Silastic capsule containing testosterone subcutaneously for 2 weeks. A series of ANI or saline injections were spaced 3 hr apart, with penile reflexes tested 6 and 12 hr after the first injection. There were no significant differences between ANI and saline-treated males at 6 hr, whereas at 12 hr ANI-treated males had significantly shorter reflex latencies and significantly more penile flips than did males injected with saline. In a final experiment (Experiment 5), the Silastic capsules were removed from the males in the previous experiment. Three injections of ANI or saline were given at 4 hr intervals beginning with the removal of the Silastic capsule.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian steroid regulation of pulsatile luteinizing hormone release during the interval between the mornings of diestrus 2 and proestrus in the rat.

The object of this study was to determine the influence of ovarian steroids on pulsatile LH release in the interval between the mornings of diestrus 2 (D2) and proestrus in the rat. Four groups of rats were bled continuously for 3 h between 09.30-12.30 h at a rate of 75 microliters whole blood/6 min: bled on D2; sham ovariectomy (OVX) on D2 and bled on proestrus; OVX on D2, implanted with empty or oil-filled capsules, and bled 24 h later; and OVX on D2, implanted with estradiol (E2) capsules, and bled 24 h later. Between D2 and proestrus, plasma E2 levels increased from 13 +/- 1 to 42 +/- 9 pg/ml, and progesterone levels decreased from 27 +/- 3 to 13 +/- 2 ng/ml, the latter reflecting the decline of the corpus luteum early on D2. Between D2 and proestrus there was no change in mean blood LH levels, LH pulse amplitude, or pulse frequency. However OVX on D2 increased mean blood LH levels 2.5-fold over values on proestrus due to a 3.5-fold elevation in LH pulse amplitude and an 80% increase in pulse frequency. E2 levels fell in these rats to 8 +/- 1 pg/ml. Restoration of physiological proestrous levels of E2 (46 +/- 5 pg/ml) significantly reduced the increase in mean blood LH levels by lowering pulse frequency to proestrous values, and by causing a 50% reduction in pulse amplitude. However, LH pulse amplitude and therefore mean blood LH levels were still higher than values on proestrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Medial preoptic area involvement in norepinephrine-induced suppression of pulsatile luteinizing hormone release in ovariectomized rats.

This study examined whether the medial preoptic area (MPOA) is a site which mediates the inhibitory effects of norepinephrine (NE) on pulsatile luteinizing hormone (LH) secretion in ovariectomized rats. Animals were bled continuously at a rate of 50 microliter whole blood/7 min for 2 h prior to push-pull perfusion in the MPOA, and during a 2-3 h period of perfusion of the MPOA (20 microliter/min) with artificial CSF, or 2 or 20 pg NE/min. In another group of rats LH levels were only determined during a 2-3 h period of MPOA perfusion with CSF. Pulsatile LH release was not affected by push-pull perfusion with CSF when a comparison was made to preperfusion LH values in the same rats. Moreover, LH levels obtained from rats only bled during MPOA perfusion with CSF were not different from LH values obtained during the preperfusion periods in the other groups. However, push-pull perfusion of the MPOA with 2 or 20 pg NE/min significantly suppressed mean LH levels by causing a 35-45% reduction in pulse frequency. No decrease occurred in LH pulse amplitude. Therefore, these studies demonstrate that NE acting at the level of the MPOA can suppress pulsatile LH release solely by decreasing LH pulse frequency.

Effect of dopamine receptor blockade or norepinephrine synthesis inhibition on acute, ovariectomy-induced increases in pulsatile luteinizing hormone release in the rat.

The initial aim of the present studies was to examine the influence of blockade of dopamine (DA) receptors with pimozide or inhibition of norepinephrine (NE) synthesis with U-14,624 on acute, ovariectomy (OVX)-induced changes in pulsatile LH release. Either treatment instituted at the time of OVX suppressed or inhibited the rapid increase in LH pulse amplitude and frequency normally occurring within 24 hr following ovarian removal on diestrus 1. While administration of pimozide at either 24 hr or 48 hr following OVX suppressed pulsatile LH release by selectively reducing LH pulse frequency, by 8 days following OVX pimozide failed to exert any effect on LH pulse frequency and therefore on pulsatile LH secretion. To determine if there was a transient critical period following OVX of at least 2 days but less than 8 when endogenous DA was excitatory to pulsatile LH release, piribedil (a DA receptor agonist) was given 24 hr following OVX. Rather than increase LH secretion, piribedil markedly suppressed pulsatile LH release indicating that DA does not stimulate LH secretion in acutely ovariectomized rats. These experiments indicate that (1) NE is involved in stimulating the acute, OVX-induced increase that occurs in pulsatile LH release; (2) DA receptor blockade by pimozide has a differential effect on pulsatile LH secretion which depends on the time following OVX when the compound is administered; (3) this differential effect cannot be explained by a transient critical period of a few days duration following OVX during which DA is excitatory to pulsatile LH release.

The influence of progesterone and estradiol on the acute changes in pulsatile luteinizing hormone release induced by ovariectomy on diestrus day 1 in the rat.

The aim of this study was to determine whether the rapid increases in LH pulse amplitude and frequency that occur within 24 h after ovariectomy (ovx) on diestrus day 1 (D1) were due to the removal of progesterone (P) and/or estradiol (E). Initial studies demonstrated that plasma levels of E and P were 18.2 +/- 1.2 pg/ml and 34.1 +/- 3.2 ng/ml, respectively, between the evening of D1 and the morning of D2 in our colony of intact rats. Immediately after ovx and jugular venous cannulation on the morning of D1, rats were implanted either with empty Silastic capsules or capsules capable of restoring physiological levels of E and P to the control values reported above. These rats were continuously bled (75 microliter/6 min) for 3 h 1 day after ovx for analysis of pulsatile LH release, and then additional plasma samples were gathered for determination of E and P levels. Rats with empty capsules had decreased levels of E and P and increases in mean blood LH levels, LH pulse amplitude, and pulse frequency. Animals with E capsules had physiological levels of E and decreased levels of P, but no suppression of the acute post-ovx increase in pulsatile LH release. In contrast, animals with P capsules had physiological plasma levels of P, decreased levels of E, and a marked reduction in the acute LH response to ovx. This suppression was due entirely to a decrease in LH pulse amplitude, as pulse frequency was not altered. Rats with E and P capsules had physiological levels of these hormones, which resulted in an even greater reduction in the acute LH response to ovx. This suppression was due to decreases in both LH pulse amplitude and pulse frequency. The effect of P on LH pulse amplitude was centrally mediated, since the in vitro response to LHRH of anterior pituitary fragments from P-implanted rats was the same as that of anterior pituitary fragments taken from rats with empty capsules. These studies demonstrate that the acute increase in LH pulse amplitude that occurs within 24 h after ovx on D1 is due to the absence of a central inhibitory effect of ovarian P, while the rapid increase in LH pulse frequency is due to the loss of both ovarian E and P.(ABSTRACT TRUNCATED AT 400 WORDS)

The role of neurotransmitters in mediating copulation-induced ovulation in the rat.

Pentobarbitone-blocked pro-oestrous rats were subjected to either limited mating (maximum of 30 mounts), all-night cohabitation with males or stimulation of the vagina and cervix with a glass rod (2 or 5 min) to determine which type of stimulus was most effective in inducing ovulation. All-night cohabitation was the most successful procedure and resulted in 100% ovulation in those rats which mated. Treatment with either phenoxybenzamine, propranolol or pimozide did not interfere with this copulation-induced ovulation whereas methysergide treatment completely blocked copulation-induced ovulation. Administration of atropine resulted in a loss of mating behaviour and these animals therefore did not ovulate. Further experiments provided evidence that administration of atropine also blocked ovulation in response to vaginal stimulation with a glass rod. Pretreatment with methysergide or atropine had no effect upon the percentage of pentobarbitone-blocked, pro-oestrous rats ovulating in response to administration of LH releasing hormone (LHRH). However, those rats given atropine shed significantly fewer ova per rat following LHRH or LH infusion when compared with controls. These results suggest that the synaptic mechanisms responsible for mediating copulation-induced ovulation are different from those mediating steroid-induced ovulation, and that ovarian cholinergic receptors may play a role in ovulation.

Acute and long-term changes in central and pituitary mechanisms regulating pulsatile luteinizing hormone secretion after ovariectomy in the rat.

These experiments examined the time course of changes in the characteristics of pulsatile luteinizing hormone (LH) secretion that occur after ovariectomy (OVX) in the rat, and compared the response of the brain and pituitary to the absence of ovarian steroid negative feedback. The literature indicates that the brain could respond to OVX by altering the frequency and/or amplitude of the pulsatile luteinizing hormone releasing hormone (LH-RH) release which triggers pulsatile LH secretion, while the pituitary could respond by altering basal LH output and/or its response to LH-RH. In vivo experiments examined changes in mean blood LH levels, LH pulse amplitudes and pulse frequencies in control rats on diestrus 1 (D1) and at 7 h, 14 h, 1, 2 or 8 days, or 3 weeks following OVX. In addition, anterior pituitaries from rats on D1 or rats ovariectomized for 1, 2 or 8 days, or 3 weeks, were incubated in vitro with or without LH-RH to examine changes in both basal and LH-RH-induced LH release. Mean blood LH levels increased within 17-24 h following OVX. This acute, rapid elevation was due to increases in both LH pulse frequency and pulse amplitude. Blood LH levels continued to increase over a 3-week period. However, the long-term increase seen at 8 days or 3 weeks was not only due to increases in LH pulse frequency and amplitude, but also to dramatic increases in basal LH secretion. The frequency of pulsatile LH release was maximal within 8 days, with no further increases occurring over the next 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary evidence for a CNS site of action for ovarian inhibin.

The ovariectomized rat bearing estrogen-containing silastic capsules underwent a primary FSH rise at 1700 hrs on all days studied. A more prolonged secondary FSH rise also occurs beginning at 2100 hrs. The primary FSH rise was attenuated or blocked by injection of charcoal-extracted porcine follicular fluid (pFF) or an extract of pFF (pFFX) limited to substances having molecular weights between 10,000 and 30,000 d. Application of pFFX directly to the dorsal anterior hypothalamic area (dAHA) by means of chronically implanted cannulas resulted in attenuation of the primary FSH rise. Similar application to medial preoptic area (mPOA) was without effect. These findings suggest that an active FSH suppressing agent, presumably ovarian inhibin, may be acting at least in part at the level of the central nervous system.