Endocrinological responses during suckling in Hatano high- and low-avoidance rats.

Hatano high-avoidance (HAA) and low-avoidance (LAA) animals were originally selected from Sprague-Dawley rats for good and poor active avoidance learning in a shuttle box. We studied the endocrinological profile in lactating rats to determine the effect of suckling during mid-lactation in HAA and LAA rats. The pups were separated from their mother rats 6 h before the onset of suckling and blood samples were drawn from unanaesthetized mother rats via a jugular cannula at 0, 5 and 15 min after the suckling stimulus and then 15, 45 and 105 min after pups were removed. Plasma concentrations of oxytocin in HAA rats were significantly higher than in LAA rats during the suckling period. Plasma concentrations of prolactin and ACTH in HAA rats were significantly higher than in LAA rats during the suckling period, and at 15 min and 45 min after the pups were removed. However, there were no strain differences in circulating corticosterone between the two lines, indicating that the response of the hypothalamo-pituitary axis to the suckling stimulus was greater in HAA rats than in LAA rats, whereas the ACTH-induced adrenal response of corticosterone release was higher in LAA rats than in HAA rats. Since dopamine from the median eminence inhibits prolactin secretion from the lactotrophs of the anterior pituitary, and tuberoinfundibular dopaminergic neurones are partially regulated by the level of circulating prolactin, we evaluated the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis. TH, measured by the accumulation of 3,4-dihydroxyphenylalanine, was significantly higher in HAA rats than in LAA rats before the suckling stimulus. After the suckling stimulus, TH activity in HAA rats was significantly lower than before suckling, whereas TH activity in LAA rats was not changed. These findings clearly demonstrated that apparent differences between the two Hatano lines exist in endocrinological profiles during suckling. These strain differences probably originate from neurotransmitter changes, such as dopamine.

Effects of phytoestrogens on acetylcholine- and isoprenaline-induced vasodilation in rat aorta.

The influence of the phytoestrogen, isoflavones, on vasodilating responses of the thoracic aorta precontracted with norepinephrine, together with the stimulatory effect on uterine weight (uterotrophic effect), was investigated in ovariectomized rats. In comparison with intact rats, acetylcholine (ACh)-induced vasodilation showed a tendency to be decreased by ovariectomy. On the other hand, isoprenaline (ISO)-induced vasodilation was significantly increased by ovariectomy. Estrogen replacement (17beta-estradiol dipropionate, 300 microg/kg per week, for 1 month) completely restored the impaired ACh- and ISO-induced vasodilation caused by ovariectomy. Dietary isoflavone aglycones (containing 52% genistein, 42% daidzein and 6% glycitein) of 157 mg/kg per day (not 67 mg/kg per day) for 1 month, in addition to the effects of estrogen replacement, completely restored the impaired vasodilation caused by ovariectomy. However, the uterotrophic effect of dietary isoflavones of 157 mg/kg per day was incomplete as compared with that by estrogen replacement. These results indicate that phytoestrogen, isoflavones, certainly possess estrogenic actions on the vasodilating responses caused by ACh and ISO, as well as a weaker uterotrophic effect.

Ultrasonic vocalization responses in genetically high- and low-emotional rats.

Tsukuba High Emotional (THE) and Tsukuba Low Emotional (TLE) strains of rats have been congenitally bred for use in studies of emotionality. The current study investigated THE and TLE strain differences in the footshock-induced ultrasonic vocalization responses of adult male rats. Ultrasonic vocalization response inducibility (ratio of rats emitting ultrasounds) and vocalization activity in THE rats were statistically higher than in TLE rats. We next examined the causal relation between the ultrasonic vocalizations and the activation of the pituitary-adrenocortical axis in response to footshocks in these two strains of rats. Rats were sorted into two groups, vocalizing and non-vocalizing, after being exposed to the shock regimen daily for 5 successive days. Basal plasma concentrations of ACTH and corticosterone were not different between THE and TLE rats. After receiving footshocks, significant increases in plasma concentrations of ACTH and corticosterone were induced in both strains of rats. These increases in plasma concentrations of ACTH and corticosterone were significantly higher in THE than in TLE rats. However, in vocalizing and non-vocalizing rats of both strains, no statistical differences in plasma concentrations of ACTH and corticosterone were observed after footshocks. These findings suggest that the high emotionality of the adult male rats was reflected in the emission of ultrasounds, and that the emission of ultrasonic vocalizations might not be related to the activation of the pituitary-adrenocortical axis.

Dexamethasone increases inhibin and estradiol secretion mediated by endogenous FSH in equine chorionic gonadotropin (eCG)-primed immature female rats.

In the present study, we have examined whether the effects of dexamethasone on follicle stimulating hormone (FSH) secretion were mediated by hypophysiotropic factors, and whether the increased levels of FSH induced by dexamethasone can stimulate ovarian functions in equine chorionic gonadotropin (eCG)-primed immature female rats. Dexamethasone (500 microg) significantly increased serum concentrations of FSH in hypophysectomized rats implanted with pituitary under the kidney capsule, as well as in intact rats. Serum concentrations of inhibin and estradiol in eCG (2.5, 5 i.u.)-primed rats were significantly increased by simultaneous treatment with dexamethasone (500 microg) and eCG. These simultaneous effects were not confirmed in hypophysectomized rats. The results had shown that hypophysiotropic factors do not mediate the selective increase of FSH secretion caused by dexamethasone. Dexamethasone induces the excess amount of FSH secretion from anterior pituitary and this FSH can stimulate inhibin and estradiol secretion in eCG-primed immature female rat.

Bisphenol A inhibits testicular functions and increases luteinizing hormone secretion in adult male rats.

Effects of a xenobiotic estrogen, bisphenol A (BPA), on reproductive functions were investigated using adult male rats. BPA was dissolved into sesame oil and injected s.c. every day (1 mg/rat) for 14 days. Animals were killed by decapitation after the final administration of BPA, and the trunk blood, pituitary, and testes were collected. Plasma concentrations of prolactin were dramatically increased and pituitary contents of prolactin were slightly increased in the BPA group compared to the control group. Plasma concentrations of testosterone were decreased and plasma concentrations of LH were increased in BPA-treated rats compared to control rats. Testicular contents of inhibin were decreased in BPA-treated rats compared to control rats, although plasma concentrations of inhibin were not changed after administration of BPA. The testicular response to hCG for progesterone and testosterone release was decreased in BPA-treated rats. Administration of BPA did not change the pituitary response to luteinizing hormone-releasing hormone (LH-RH) in castrated male rats treated with testosterone. Male sexual behavior also was not changed as a result of BPA treatment. These results suggest that BPA directly inhibits testicular functions and the increased level of plasma LH is probably due to a reduction in the negative feedback regulation by testosterone. The testis is probably a more sensitive site for BPA action than the hypothalamus-pituitary axis.

Antagonist of pituitary adenylate cyclase activating polypeptide suppresses prolactin secretion without changing the activity of dopamine neurons in lactating rats.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a relatively new neuropeptide, and it has a potent stimulatory effect on adenylate cyclase activity in rat pituitary cells. However, the role of PACAP in the physiological control of prolactin (PRL) secretion is still unclear. In the present study, we investigated the physiological significance of endogenous PACAP on PRL secretion in lactating rats. On lactation days 7-8, pups were separated from their mother rats for 5 h before the onset of suckling and PACAP6-38 (16 microg), a receptor antagonist, was injected through the lateral ventricle cannula just after the removal of pups. The effects of PACAP6-38 on PRL and oxytocin secretion, and on the activity of tyrosine hydroxylase (TH), were examined after the onset of suckling. Administration of PACAP6-38 inhibited PRL levels in response to suckling, but it did not affect the activity of TH, as measured by DOPA accumulation at 15 min after administration of NSD 1015 (25.0 mg/kg), an L-aromatic amino acid decarboxylase inhibitor, or the plasma concentrations of oxytocin in lactating rats. Injection of alpha-methyl-p-tyrosine (alpha-MT; 50 mg/kg), an inhibitor of dopamine synthesis, increased PRL levels, and suckling caused a further increase in the plasma concentrations of PRL. An injection of PACAP6-38 (i.c.v.) also inhibited the PRL response to suckling under dopamine depletion. These results suggest that endogenous PACAP acts as a neurotransmitter or neuromodulator within the hypothalamus and plays an important role for PRL secretion in lactating rats. Endogenous PACAP may regulate PRL secretion, possibly mediated by PRL-releasing factors such as vasoactive intestinal polypeptide or vasopressin.

Dynamic changes in plasma concentrations of gonadotropins, inhibin, estradiol-17beta and progesterone in cows with ultrasound-guided follicular aspiration.

To elucidate the effects of ultrasound-guided transvaginal follicular aspiration, plasma concentrations of FSH, LH, inhibin, estradiol-17beta and progesterone, and folliculogenesis were examined in Holstein cows. Four clinically healthy cows with regular estrous cycles were scanned by ultrasound per rectum once a week for 9 weeks before the commencement of follicular aspiration. All visible follicles were divided into 3 categories based on their sizes (2 < or = small < 5 mm; 5 < or = medium < 10 mm, large > or = 10 mm). The follicular aspiration was started at random during the estrous cycle and conducted under epidural anesthesia induced with 5 ml of 2% lidocaine once a week for 6 weeks. The average number of total visible follicles > or = 2 mm in diameter at 7 days after aspiration (21.7 +/- 7.4, n = 24) was similar to that before starting aspiration (26.7 +/- 10.5, n = 36). Plasma inhibin and estradiol-17beta declined and fell to a trough on 1.5 days and returned to pre-aspiration values by 5 days after aspiration. Plasma concentrations of FSH increased and reached peak levels between 1 and 1.5 days after aspirations. Plasma concentrations of LH also increased and reached peak levels between 0.5 and 1.5 days after aspirations. Both plasma FSH and LH had returned to pre-aspiration levels by 5 days after aspirations. Plasma concentrations of progesterone did not change with the follicular aspiration. These results demonstrate that follicular aspiration decreases plasma concentrations of inhibin and estradiol-17beta, which in turn leads to a rise in plasma concentrations of FSH and LH. It is suggested that marked increases in plasma concentrations of FSH and LH after the aspiration stimulate the development and maturation of a new cohort of follicles within one week in cows.

Hypothyroidism increases prolactin secretion and decreases the intromission threshold for induction of pseudopregnancy in adult female rats.

In order to understand the mechanism by which thyroid hormones alter prolactin (PRL) secretion, we investigated the role of tuberoinfundibular dopamine (TIDA) neurons and pituitary and hypothalamus vasoactive intestinal peptide (VIP) in thiouracil- (0. 03% in drinking water for 16 days) induced-hypothyroid adult female rats. The intromission threshold for induction of pseudopregnancy also was examined to evaluate the PRL response to coital stimulation in hypothyroid rats. Hypothyroidism in adult female rats did not affect TIDA neuronal activity as measured by tyrosine hydroxylase activity (DOPA accumulation 30 min after administration of m-hydroxybenzylhydrazine dihydrochloride, 100 mg/kg, i.p.) in the stalk-median eminence compared with that in euthyroid rats, whereas pituitary concentration of VIP was dramatically increased. Plasma concentration of PRL was higher at 1100 h of proestrus and estrus in hypothyroid rats as compared with that of euthyroid rats. The proportion of female rats exhibiting pseudopregnancy was higher in hypothyroid animals (100%) receiving seven intromissions than in euthyroid animals (43%). Administration of L-thyroxine in hypothyroid rats decreased the proportion of pseudopregnancy (40%) to the level of euthyroid animals. These results indicate that the increased level of pituitary VIP probably affects PRL secretion in a paracrine or autocrine manner and account for the hyperprolactinemia induced in hypothyroid female rats. No role for TIDA neurons in PRL elevation can be ascribed. A decrease in the intromission threshold for induction of pseudopregnancy might be due to increased levels of PRL in hypothyroid female rats.

Calcitonin inhibition of prolactin secretion in lactating rats: mechanism of action.

The effects of intracerebroventricular (10 ng/rat) or intravenous (10 or 40 microg/15 min/rat) administration of salmon calcitonin (sCT) on the prolactin (PRL) response to suckling and the activity of tyrosine hydroxylase (TH) were examined in lactating rats. Plasma concentration of PRL increased dramatically in control rats after the onset of the suckling stimulus, while administration of sCT resulted in inhibition of PRL response to suckling. The action of sCT was much more effective with intracerebroventricular administration, which totally blocked PRL release, compared to intravenous administration. The intracerebroventricular administration of sCT increased TH activity of tuberoinfundibular dopamine neuron (TIDA) in the stalk-median eminence, as measured by DOPA accumulation, while completely suppressing the PRL response to suckling. Injection of alpha-methyl-p-tyrosine (alpha-MT; 50 mg/kg), an inhibitor of TH and thus dopamine synthesis, increased PRL levels, and suckling caused a further increase in plasma concentrations of PRL. Injection of sCT (intracerebroventricularly) did not inhibit the PRL response to suckling in the presence of a depletion of dopamine. These results suggest that sCT inhibition of PRL secretion in lactating rats is mediated mainly by TIDA neurons without involvement of other neuroendocrine mechanisms.

Postnatal behavior in hatano high- and low-avoidance rats following prenatal exposure to low-dose methylazoxymethanol.

The hypothesis that genetic factors influence behavioral effects was tested in rats exposed prenatally to methylazoxymethanol (MAM). We examined whether baseline behavior is an important factor influencing behavioral effects, and whether a behaviorally selected strain was useful for study of neurobehavioral teratology. Pregnant high- and low-avoidance animals (HAAs and LAAs) of the Hatano strain, selectively bred for high and low shuttlebox avoidance responses, respectively, were given an IP injection of a low dose of MAM (15 mg/kg) on day 14 of gestation. The offspring of these animals were subjected to behavioral tests for locomotor activity (running-wheel and open-field tests) and learning ability (Biel maze and shuttlebox avoidance tests). There were no significant effects of MAM on running-wheel activity or shuttlebox avoidance learning, whereas the number of errors in the Biel maze was increased in the MAM offspring of both strains. Interestingly, open-field activity of the MAM offspring was markedly decreased in LAAs but not in HAAs. Therefore, an additional experiment was performed to determine plasma levels of ACTH and corticosterone following open-field exposure. When compared to control offspring of the respective strains, plasma levels of ACTH and corticosterone were not altered by prenatal MAM treatment in LAAs. Instead, the MAM offspring in HAAs exhibited decreased ACTH levels in absence of behavioral alterations. These results demonstrated that prenatal exposure to low doses of MAM may alter postnatal behavior and endocrine response of the offspring, although to a differing degree in HAAs and LAAs. Our observations suggested that behaviorally selected strains are sensitive to neurobehavioral teratogens such as MAM.

Interleukin-6 decreases estrogen production and messenger ribonucleic acid expression encoding aromatase during in vitro cytodifferentiation of rat granulosa cell.

To elucidate the influence of interleukin-6 (IL-6) on the maturation of rat granulosa cell (GC), we have established a differentiation model of rat GC in vitro and examined the expression of IL-6 and its receptors, and its possible actions during GC maturation. Bioactive IL-6 was detectable in the conditioned media of GC at approximately 2.5 ng/ml/24 h per 5x10(5) cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that messenger RNAs encoding components of functional IL-6 receptor, namely both ligand-binding subunit (IL-6R) and gp130, were expressed in GC. Treatment of GC with IL-6 for 72 h during the process of in vitro GC maturation dose-dependently inhibited the accumulation of estradiol-17beta (E(2)) and the expression of cytochrome P450 aromatase (P450arom). IL-6 did not change nitric oxide (NO) production and inducible NO synthase expression, implying that IL-6-induced suppression on E(2) levels is dissociated with NO expression. Further, GC which had been incubated with neutralizing anti-IL-6 antibody showed a distinct increase in the levels of P450arom mRNA. These results suggest that IL-6 may attenuate E(2) production partially by inhibiting the expression of aromatase mRNA as an intraovarian regulator for suppressing GC maturation.

Dexamethasone or triamcinolone increases follicular development in immature female rats.

We have previously reported that dexamethasone increased follicle-stimulating hormone (FSH) secretion via suppression of inhibin in immature female rats. In the present study, we investigated the effects of dexamethasone or triamcinolone on follicular development and ovarian functions (estradiol and inhibin secretion) in equine chorionic gonadotropin (eCG)-primed immature female rats. Dexamethasone significantly increased the number of ovulated oocytes in immature female rats treated with 5 i.u. eCG. Serum concentration of FSH in eCG-treated female rats was increased by administration of dexamethasone or triamcinolone, showing the peak value at 9 h after its administration, although the levels of inhibin markedly decreased at that time. Serum concentrations of inhibin and estradiol in eCG-treated female rats increased at 24 h after administration of dexamethasone or triamcinolone. These results demonstrate that dexamethasone or triamcinolone increases FSH secretion, and the excess amount of FSH strongly stimulates follicular development cooperating with exogenous eCG.

Dexamethasone increases follicle-stimulating hormone secretion via suppression of inhibin in rats.

In the present study, the effects of dexamethasone on follicle-stimulating hormone (FSH) secretion in immature female rats were investigated. Dexamethasone increased the selective secretion of FSH and decreased plasma concentrations of inhibin in immature female rats. The effects of dexamethasone on FSH secretion were not confirmed in rats treated with ovariectomy or immunoneutralization against inhibin. In addition to the direct effect of dexamethasone on FSH synthesis in gonadotrophs, the present study has clearly demonstrated that the increased level of FSH in dexamethasone-treated rats is mediated by suppression of ovarian function, especially by the inhibition of inhibin secretion.

Plasma ACTH levels during early, two-way avoidance acquisition in high- and low-avoidance rats (Hatano strains).

Having successfully bred for high- and low-avoidance rats (HAA and LAA, respectively) on a shuttlebox task, we performed three experiments designed to identify factors which might be related to the phenotypic differences seen in avoidance behavior. In experiment 1, shuttlebox behavior was measured to determine whether the phenotypic difference was activity related. In terms of intertrial responses, there was no difference between HAA and LAA rats in locomotor activity during the conditioning process. Experiment 2 compared adrenal weights of HAA and LAA rats at 11 weeks of age. The observation that the adrenal glands were heavier in HAA than in LAA rats suggested that these strains might differ in aspects of endocrine response. In experiment 3, plasma levels of ACTH and corticosterone were determined during early escape/avoidance acquisition in the shuttlebox. Plasma levels of ACTH after the shuttlebox testing were higher in HAA than in LAA rats. There was no difference between the two strains in plasma levels of corticosterone after testing, possibly due to a ceiling effect. These results suggest that the phenotypic differences in the acquisition of avoidance behavior of HAA and LAA rats may be related to different endocrine responses, rather than to locomotor activity.

Inhibin secretion in the mare: localization of inhibin alpha, betaA, and betaB subunits in the ovary.

To determine the source of circulating inhibin and estradiol-17beta during the estrous cycle in mares, the cellular localization of the inhibin alpha, betaA, and betaB subunits and aromatase in the ovary was determined by immunohistochemistry. Concentrations of immunoreactive (ir-) inhibin, estradiol-17beta, progesterone, LH, and FSH in peripheral blood were also measured during the estrous cycle in mares. Immunohistochemically, inhibin alpha subunits were localized in the granulosa cells of small and large follicles and in the theca interna cells of large follicles, whereas inhibin betaA and betaB subunits were localized in the granulosa cells and in the theca interna cells of large follicles. On the other hand, aromatase was restricted to only the granulosa cells of large follicles. Plasma ir-inhibin concentrations began to increase 9 days before ovulation; they remained high until 2 days before ovulation, after which they decreased when the LH surge was initiated. Thereafter, a further sharp rise in circulating ir-inhibin concentrations occurred during the process of ovulation, followed by a second abrupt decline. After the decline, plasma concentrations of ir-inhibin remained low during the luteal phase. Plasma estradiol-17beta concentrations followed a profile similar to that of ir-inhibin, except during ovulation, and these two hormones were positively correlated throughout the estrous cycle. Plasma FSH concentrations were inversely related to ir-inhibin and estradiol-17beta. These findings suggest that the dimeric inhibin is mainly secreted by the granulosa cells and the theca cells of large follicles; granulosa cells of small follicles may secrete inhibin alpha subunit, and estradiol-17beta is secreted by the granulosa cells of only large follicles in mares.

Influence of thiouracil-induced hypothyroidism on adrenal and gonadal functions in adult female rats.

The effect of hypothyroidism on adrenals and gonads in adult female rats was investigated throughout the estrous cycle. Hypothyroidism was induced by administration of 4-Methyl-2-Thiouracil (Thiouracil) in the drinking water. The weight of ovaries and adrenals, and the plasma levels of corticosterone decreased in hypothyroid rats as compared with euthyroid rats throughout the estrous cycle. Hypothyroidism resulted in decreased concentrations of plasma LH on the day of diestrus and proestrus, whereas the plasma concentrations of prolactin and progesterone increased as compared with euthyroid rats. The weight of uteri and plasma concentrations of estradiol decreased during the day of diestrus and proestrus in hypothyroid rats as compared with euthyroid rats. To further clarify the dysfunction of hypothalamo-hypophysial-adrenal axis in hypothyroid rats, animals were stressed by immobilization for 3 hr. In hypothyroid rats, a marked increase in plasma levels of ACTH in response to immobilization stress was observed compared to euthyroid control, whereas increases in plasma concentrations of corticosterone were much smaller in hypothyroid than euthyroid rats. These results clearly indicate that hypothyroidism causes both gonadal and adrenal disturbances in adult female rats. The increased concentrations of plasma progesterone may be due to hypersecretion of prolactin during the day of proestrus and estrus, which in turn result in disruption of the estrous cycle.

Effects of thyroidectomy or thiouracil treatment on copulatory behavior in adult male rats.

Male copulatory behavior and the function of the hypothalamo-hypophysial-gonadal axis in hypothyroid male rats were investigated in the present study. Hypothyroidism was induced by thyroidectomy or thiouracil. In male copulatory behavior test, intromission latencies in hypothyroid rats were significantly longer than those in euthyroid rats and ejaculation frequencies were reduced in hypothyroid male rats compared to control rats without reduction of plasma concentrations of testosterone. These changes in copulatory behavior in hypothyroid male rats were restored to control levels by administration of T4 (5 micrograms/rat). Hypothyroidism decreased adrenal weights, and basal and peak concentrations of corticosterone during diurnal variation, whereas it increased peak concentrations of ACTH in adult male rats. These results indicate that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of ACTH. The adrenal disturbance observed in hypothyroid rats may affect male copulatory behavior.

Hypersecretion of corticotrophin-releasing hormone and arginine vasopressin in hypothyroid male rats as estimated with push-pull perfusion.

The relationship between hypothyroidism and disturbance of the hypothalamo-hypophysial-adrenal axis was investigated using adult male rats. Hypothyroidism was produced by administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Hypothyroidism decreased adrenal weights to 57% of controls and plasma concentrations of corticosterone to 48% of controls. The changes in the weight of adrenals recovered to control levels by administration of thyroxine. The pituitary responsiveness to corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) for ACTH release markedly increased in hypothyroid rats as compared with euthyroid rats. In vivo release of CRH and AVP in median eminence significantly increased in hypothyroid rats as compared with euthyroid rats. There were no significant differences in hypothalamic concentrations of CRH and AVP. These results indicate that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of ACTH mediated by increases in synthesis of CRH and AVP in the hypothalamus.

Effects of repeated ether stress on the hypothalamic-pituitary-testes axis in adult rats with special reference to inhibin secretion.

Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male rats were examined. To clarify the role of adrenal glucocorticoids in gonadal function, the effects of adrenalectomy and Dexamethasone treatment were also investigated. Ether stress increased the plasma concentrations of ACTH and corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and testosterone. The pituitary responsiveness to LH-RH for LH release and testicular responsiveness to the endogenous LH for testosterone release were maintained in stressed rats. Adrenalectomy caused an increase in the plasma concentrations of ACTH, but decreased the plasma concentrations of LH, FSH and testosterone. Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma gonadotropins to control levels. The concentration of plasma inhibin did not change in adrenalectomized rats, but it was decreased compared to control rats by Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted in a decline in plasma levels of testosterone and inhibin without a decrease in the levels of LH and FSH, indicating the direct effect of Dexamethasone on the testes. These results indicate that increased ACTH secretion in stressed rats is probably due to hypersecretion of CRH from the hypothalamus, which suppresses gonadotropin secretion via the inhibition of LH-RH. The decreased levels of testosterone may be caused by a stress-induced decrease in plasma LH concentrations and increased secretion of corticosterone in the ether stressed rats. The low levels of plasma inhibin in stressed rats was also probably due to the direct effect of corticosterone on the Sertoli cells.

Adrenal and gonadal function in hypothyroid adult male rats.

The functional relationship between thyroid, adrenal and gonadal hormones was investigated using adult male rats. Hypothyroidism was produced by the administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Plasma concentrations of TSH dramatically increased, whereas plasma concentrations of tri-iodothyronine and thyroxine decreased in thiouraciltreated rats as compared with euthyroid rats. Hypothyroidism increased basal levels of plasma ACTH and pituitary content of ACTH. The pituitary responsiveness to CRH for ACTH release markedly increased, whereas the adrenal responsiveness to ACTH for corticosterone release decreased. These results indicated that hypothyroidism causes adrenal dysfunction in adult male rats. Pituitary contents of LH and prolactin decreased in hypothyroid rats as compared with euthyroid rats. In addition, hypothyroidism lowered pituitary LH responsiveness to LHRH. Testicular responsiveness to human chorionic gonadotrophin for testosterone release, however, was not different between euthyroid and hypothyroid animals. These results indicated that hypothyroidism causes adrenal dysfunction and results in hypersecretion of ACTH from the pituitary gland. Adrenal dysfunction may contribute to the inhibition of LHRH secretion from the hypothalamus, possibly mediated by excess CRH.