Effects ofaxenoblotlc estrogen, blsphenol A (SPA), on reproductive functions were Investigated using adult male rats. SPA was dissolved Into sesame 011 and Injected sc every day (1 mglrat) for 14 days. Animals were killed by decapitation after the final administration of SPA, 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 SPA group compared to the control group. Plasma concentrations of testosterone were decreased and plasma concentrations of LH were increased In SPA-treatedrats compared to control rats. Testicular contents of Inhlbln were decreased In SPA-treated rats compared to control rats, although plasma concentrations of Inhlbln were not changed after administration of SPA. The testicular response to hCG for progesterone and testosterone release was decreased In SPA-treated rats. Administration of SPA did not change the pituitary response to luteinizing hormonereleasing hormone (LH-RH) In castrated male rats treated with testosterone. Male sexual behavior also was not changed as a result of SPA treatment. These results suggest that SPA 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 SPA action than the hypothalamus-pituitary axis.

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.

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.

Abstract. In order to clarify the functional relationship between thyroid, adrenal and gonadal hormones, hypothyroidism was induced by administration of thiuoracil in adult male and female rats, and the effects of hypothyroidism on the adrenal and the gonadal axes were investigated in the present study. 1. The functional relationship between thyroid and adrenal hormones: Adrenal weights and corticosterone were lowered, whereas the secretion of ACTH, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) increased in hypothyroid rats compared to euthyroid rats. These results indicate that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of CRH and AVP from the hypothalamus. 2. The functional relationship between thyroid and gonadal hormones: The pituitary response to LHRH was lowered, whereas the testicular response to hCG was not changed in hypothyroid rats. Hypothyroidism suppressed copulatory behavior in male rats. These results suggest that hypothyroidism probably causes dysfunction in gonadal axis at the hypothalamic-pituitary level in male rats. In adult female rats, hypothyoidism inhibited the follicular development accompanied estradiol secretion, whereas plasma concentrations of progesterone and prolactin (PRL) increased in hypothyroid female rats. Hypothyroidism significantly increased the pituitary content of vasoactive intestinal peptide (VIP) though it did not affect dopamine synthesis. These results suggest that hypothyroidism increases pituitary content of VIP and this increased level of VIP likely affects PRL secretion in a paracrine or autocrine manner. In female rats, inhibition of gonadal function in hypothyroid rats mediated by hyperprolactinemia in addition to hypersecretion of endogenous CRH.

ABSTRACT. 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. -KEY WORDS: adrenal, gonad, hyperprolactinemia, hypothyroidism.J. Vet. Med. Sci. 60(4): 439-446, 1998 hypothyroidism on these two axes throughout the estrous cycle in adult female rats. MATERIALS AND METHODS Animals and treatments:Adult female Wistar-Imamichi rats (The Imamichi Institute for Animal Reproduction, Ibaraki, Japan) were used throughout the present study. Animals were maintained on a 14 hr light and 10 hr dark lighting schedule (light on at 05:00 hr). The room was kept at 23-26°C. They received a standard laboratory diet and water ad libitum. Hypothyroidism was induced by administration of 0.03% 4-Methyl-2-Thiouracil (Thiouracil: Wako Pure Chemical Industries, Ltd. Osaka, Japan) in the drinking water. We have confirmed the effectiveness of Thiouracil in our previous study [35]. Each rat of all experimental group was confirmed vaginal smear every day during administration of Thiouracil (until 32 days after administration of Thiouracil for first group (20 rats) and 16 days after treatment for second group (160 rats). At the 4th estrous cycle (16 days after the initiation of Thiouracil treatment), 5 animals of each group (total 160 adult female rats) were sacrificed by decapitation every 6 hr throughout 4-day estrous cycle. Trunk blood was collected and centrifuged immediately and plasma was separated and stored at 20°C until assayed tri-iodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), LH, FSH, prolactin (PRL), estradiol, progesterone, adrenocorticotropic hormone (ACTH) and corticosterone. After the decapitation, ov...