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Biomedical subjects

K Taya

Publications and source records attributed to K Taya.

At least 37 records · Page 2Linked to original sources

Preovulatory follicles in the ovary as the source of circulating inhibin in the duck.

Inhibin secretion in the adult female duck was investigated. The bovine inhibin radioimmunoassay (RIA) system and human enzyme-linked immunosorbent assay (ELISA) of inhibin A and inhibin B were first validated for use in the duck. In both RIA and ELISA, the dilution curves of plasma and homogenate of the first largest follicle (F1) were parallel to each standard curve, indicating that plasma and the F1 follicle contained immunoreactive (ir) and dimeric inhibins. Short-term food deprivation caused follicular atresia in the ovary and significantly depressed the plasma concentration of ir-inhibin. Positive immunostaining for inhibin alpha-, betaA-, and betaB-subunits was clearly detected in the granulosa cells of the four largest preovulatory follicles. Immunolocalization of these three inhibin subunits was also weakly seen in the interna theca cells of these follicles. These results demonstrate that inhibin alpha-, betaA-, and betaB-subunit proteins are colocalized in the granulosa cell and theca cell of the four largest preovulatory follicles in the duck ovary. The present results, therefore, indicate that the four largest follicles in the ovary are the main source of circulating inhibin in the female duck.

Animals↗

Immunohistochemical localization of inhibin subunits in the testis of the bull.

The differential localization of the inhibin beta subunits betaA and betaB in the testis of adult bull was studied using specific monoclonal and polyclonal primary antibodies. Inhibin betaA- and betaB-subunits were localized only in the Sertoli cells. The inhibin betaA-subunit was observed in the cytoplasm while the betaB-subunit was localized in the nucleus. No specific findings depending on spermatogenic stages were observed among the seminiferous tubules. Moreover, the inhibin alpha-subunit was not detected in the testis of the bulls. In addition, no inhibin subunits were detected in the Leydig cells and spermatogenic cells. These findings indicate the presence of betaA- and betaB-subunits in the bull, which may suggest a possibility that activin is produced and/or stored in the Sertoli cells and regulates spermatogenesis in an autocrine/paracrine manner. Moreover, the inhibin betaB-subunit may be produced in the nucleus but the functional meaning of this is not yet clear.

Animals↗

An ovarian interstitial cell hamartoma in a newborn foal.

A case of congenital ovarian interstitial cell hamartoma in a thoroughbred foal that died of apparent nutritional myopathy (white-muscle disease) 14 h after birth is described. An incidental finding at necropsy was a pale brown, mushroom-shaped, pedunculated mass (6 x 4 x 3 cm) attached to the left ovary. On the cut surface, the mass had a peripheral rim of dense parenchyma (3-5 mm wide), surrounding a pale gelatinous core. Histologically, the mass consisted of a peripheral zone of densely packed large cells that were quite similar, morphologically, to fetal ovarian interstitial cells, and a central area of small nests of similar cells scattered within an extremely loose connective tissue matrix. Immunohistochemically, intracytoplasmic positive labelling for inhibin was detected in these cells. These observations suggest that the lesion was an ovarian interstitial cell hamartoma.

Animals↗

Contribution of endogenous inhibin to the decline of the secondary surge of follicle-stimulating hormone in the rat.

The involvement of inhibin in the decline of the secondary surge of follicle-stimulating hormone (FSH) was investigated in the rat. After ovariectomy or treatment with inhibin antiserum conducted at 2300 hours during pro-oestrus, plasma concentrations of FSH were maintained at high levels compared with control rats. However, plasma FSH started to decline at 0500 hours during oestrus in both the groups. The same treatments conducted during metoestrus markedly increased plasma FSH after 24 h (twofold compared with the treatments during pro-oestrus), suggesting that the treatments sufficiently depleted circulating inhibin. To examine whether the decline of plasma FSH occurred through a transcriptional mechanism or through a translational mechanism, FSH-beta mRNA expression and the pituitary concentration of FSH were measured. Neither ovariectomy nor inhibin immunization conducted during the night of pro-oestrus, affected the pituitary concentration of FSH after 24 h, whereas a noticeable increase was observed after the treatments conducted during metoestrus. In both stages, both ovariectomy and inhibin immunization significantly increased FSH-beta mRNA expression compared with control rats. In contrast with the pituitary concentration of FSH, the effect of inhibin immunization on FSH-beta mRNA expression was not different between the stages. The present data demonstrate the involvement of inhibin in the decline of the secondary surge of FSH, and suggest that a factor or factors other than inhibin may also be responsible for the fall in FSH. Changes in the pituitary concentration of FSH and FSH-beta mRNA expression suggest that post-transcriptional mechanisms may be involved in the suppression of FSH secretion during oestrus.

Animals↗

Exposure of neonatal female rats to p-tert-octylphenol disrupts afternoon surges of luteinizing hormone, follicle-stimulating hormone and prolactin secretion, and interferes with sexual receptive behavior in adulthood.

The present study investigated the effects of exposure of neonatal female rats to p-tert-octylphenol (OP) on estrogen-induced afternoon surges of LH, FSH, and prolactin (PRL) secretion, and on sexual behavior in adulthood. After birth, one group of female Wistar rat pups received s.c. injections of OP (100 mg/kg body weight [BW]; OP group) dissolved in DMSO, while the control group received DMSO only (DMSO group). In order to make a qualitative comparison, a third group was injected with estradiol-17beta (500 microg/kg BW; estradiol group) dissolved in DMSO. Injections were given on Days 1, 3, 5, 7, 9, 11, 13, and 15 of age. The rats from the OP and estradiol groups that were used for subsequent experiments were in persistent vaginal estrus. Spontaneous LH surge measured at Postnatal Days (PND) 78-81 was observed only in the DMSO group on the afternoon of the day of proestrus. At PND 115, randomly selected rats from each of three treatment groups were bilaterally ovariectomized (ovx), and 8 days later, Silastic capsules containing estradiol-17beta were implanted under the skin. Estrogen implants stimulated afternoon surges of LH, FSH, and PRL for two consecutive days in the DMSO group, but not in the OP and estradiol groups. Rats from the OP and DMSO groups underwent ovx at PND 186, and 6 days later they were treated with a combination of estradiol benzoate s.c. (15 microg/kg BW) and progesterone s.c. (2 mg/kg BW) to test the lordosis reflex. In response to this hormone treatment and mounting stimulus delivered by the stud male rats, the OP-treated rats were less receptive compared with control DMSO-treated rats, and thus the lordosis quotient and lordosis rating were significantly (P < 0.05) reduced in the OP group compared with the DMSO group. Analysis of the area of the sexually dimorphic nucleus of the preoptic area of the brain revealed that the area of this nucleus was larger in the OP group than it was in control DMSO rats. We conclude that the exposure of neonatal female rats to higher doses of OP disrupts the cyclic release of LH, FSH, and PRL, and interferes with the display of sexual receptive behavior in adulthood.

Aging↗

Production and endocrine role of inhibin during the early development of bull calves.

This study investigated the ontogeny of control of FSH secretion by inhibin during early prepubertal development of bulls by 1) measurements of circulating levels of inhibin and FSH from 1 to 13 wk of age, and 2) immunoneutralization of endogenous inhibin at 7, 21, 60, and 120 days of age. In addition, production and localization of inhibin in testes were examined by immunohistochemistry and Western blots at 7, 21, 60, and 120 days of age. Plasma immunoreactive inhibin levels were relatively low between 1 and 3 wk of age and then showed a tendency to rise (P < 0.1) from 4 wk of age. Circulating concentrations of FSH were low during 3 wk after birth and increased at 5 wk, remained high (P < 0.05) until 16 wk of age. Treatment with inhibin antiserum resulted in a significant (P < 0.05) increase in plasma FSH at 7, 21, 60, and 120 days of age compared to those following injection of control serum; however, the magnitude of the FSH rise after inhibin immunization was greater as bulls aged. There were no significant changes in plasma LH after inhibin immunization. An intense staining of inhibin alpha subunits was found in Sertoli cells within the solid seminiferous cords from 7 to 120 days of age, while no specific immune reaction was found in interstitial cells. Western blot analysis of testicular homogenates isolated from bulls 7-120 days of age revealed presence of a 28.5-kDa molecule that cross-reacted with inhibin alpha subunit and beta(B) subunit-specific antibodies. In this study, before 13 wk of age in bull calves, there was no inverse relationship between plasma concentrations of immunoreactive inhibin and FSH. However, the present immunization study clearly indicates that inhibin participates in the regulation of FSH secretion from infancy to early prepubertal stage, although the endocrine significance of inhibin becomes greater in older bulls. The results also indicate that the major production site of inhibin in the testis is Sertoli cells and that these cells produce inhibin that exerts a negative feedback effect on FSH secretion from early stages of development.

Aging↗

Changes in sex steroids, gonadotropins, prolactin, and inhibin in pregnant and nonpregnant Japanese black bears (Ursus thibetanus japonicus).

We examined changes in the concentrations of serum progesterone (P4), estradiol-17beta (E2), FSH, LH, prolactin (PRL), and inhibin to determine their interaction and their effect on the reproductive endocrine controls of pregnant and nonpregnant female Japanese black bears. Fourteen female bears were used in this study over a 2-yr period. In the first year, six of the bears were divided into two groups; a pseudopregnant group and a nonpregnant group. In the second year, the remaining eight bears were also divided into two groups; a pregnant group and a nonpregnant group. Pregnant and pseudopregnant bears had similar P4 trends with both groups exhibiting a significant increase in December, which is the suspected time of implantation in pregnant bears. These trends correlated with an increase in PRL levels, whereas low levels of LH were maintained throughout the year. Nonpregnant bears maintained low concentrations of P4, and compared with pregnant and pseudopregnant bears, they also exhibited a delayed elevation in PRL. Luteinizing hormone activity varied among individual animals, but regardless of reproductive status, fluctuation patterns of E2, FSH, and inhibin did not differ among bears. Our results suggest that PRL may play a luteotropic role in both pregnant and pseudopregnant bears, and is possibly responsible for inducing reactivation of the dormant corpus luteum that precedes implantation in the Japanese black bear.

Animals↗

Regulation of follicle-stimulating hormone secretion by estradiol and dimeric inhibins in the infantile female rat.

Plasma and ovarian levels of the dimeric forms of inhibin and plasma estradiol-17beta were investigated and compared with changes in plasma gonadotropins from Postnatal Day (PND) 5 to PND 30 in the female rat. The inhibin subunit proteins were localized in follicular granulosa cells of the ovary. Plasma immunoreactive inhibin levels were low until PND 15 and increased thereafter. Plasma levels of inhibin B (alpha and beta(B) subunits) remained very low until PND 15 and then increased by approximately 24-fold. In contrast, plasma levels of inhibin A (alpha and beta(A) subunits) were relatively low and steady until PND 20, then increased by approximately 3-fold at PND 25. Changes in ovarian inhibin A and B levels closely resembled those in plasma levels. Plasma FSH levels were low at PND 10 but started to peak from PND 15 and remained high until PND 20, followed by a remarkable reduction at PNDs 25 and 30. This dramatic fall in FSH coincided with the rise of inhibin A. A significant inverse correlation was observed between plasma FSH and plasma inhibin A (r = -0.67, P < 0.0002), ovarian inhibin A (r = -0.48, P < 0.01), plasma inhibin B (r = -0.48, P < 0.05), and ovarian inhibin B (r = -0.54, P < 0.01). Plasma estradiol-17beta levels were elevated from PND 5 through PND 15, then fell sharply through PND 30. Plasma estradiol-17beta was significantly and positively (r = 0.75, P < 0.0002) correlated with plasma FSH. Plasma LH rose to higher levels at PND 15 and tended to be lower thereafter. The inhibin alpha, beta(A), and beta(B) subunits were localized to primary, secondary, and antral and large antral follicles, but the types of these immunopositive follicles varied with age. It appeared that, at PND 25 and afterward, all three subunits were mainly confined to large antral follicles in the ovary. We conclude that estradiol-17beta likely is the major candidate in stimulation of FSH secretion in the infantile female rat. We also conclude that inhibin regulation of pituitary FSH secretion through its negative feedback in the infantile female rat begins to operate after PND 20. We suggest that this negative feedback is achieved by increases in plasma levels of the two dimeric forms, and that inhibin A appears to be the major physiological regulator of FSH secretion at the initiation of this mechanism. We also conclude that large antral follicles in the ovary are the primary source of these bioactive inhibins that are secreted in large amounts into the circulation after PND 20.

Aging↗

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.

Animals↗

Regulatory role of inhibin in follicle-stimulating hormone secretion and folliculogenesis in the guinea pig.

The effects of unilateral and bilateral ovariectomy and passive immunization against inhibin on follicle-stimulating hormone (FSH) secretions and follicular development in the guinea pig were investigated. Bilateral ovariectomy decreased plasma immunoreactive (ir-) inhibin rapidly and increased plasma FSH significantly. Unilateral ovariectomy decreased plasma ir-inhibin and increased plasma FSH temporarily, and doubled the number of ova released from the remaining ovary at the subsequent ovulation in guinea pigs. Injection of 1.0 ml inhibin antiserum significantly increased concentrations of plasma FSH at 6 hr onwards and the number of small follicles (100-200 microm in diameter) at 48 hr after the injection in guinea pigs bearing progesterone-containing implants. In vitro bioassay showed that inhibin antiserum could neutralize the suppression of ovarian homogenate on FSH secretion from cultured rat anterior pituitary cells. These results confirm the evidence that the ovary is the main source of inhibin secretion and both in vitro bioassay and passive immunization against inhibin show that the inhibin is a major regulator in the follicular development through FSH secretion in guinea pigs.

Animals↗

Prepubertal changes in immunoreactive inhibin concentration in blood serum and testicular tissue in Holstein bull calves.

Age-related changes in immunoreactive inhibin (ir-inhibin) levels and the relationship among ir-inhibin, gonadotropins and testosterone were examined in 53 Holstein bull calves from neonates to 8.6 months old. Serum levels of ir-inhibin, luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone, as well as ir-inhibin levels in testicular extracts, and testicular sizes were measured. All hormones were measured by specific radioimmunoassays. The concentrations of ir-inhibin in serum and testicular tissue were high in neonatal calves and tended to decrease with age. In contrast, serum concentrations of gonadotropins did not show any age-related changes within the experimental period. Serum testosterone levels and testicular sizes (length, width and weight) were positively correlated with age. Furthermore, a positive immunostaining to antiserum for the inhibin alpha-subunit was immunocytochemically observed only in Sertoli cells of the seminiferous tubules from neonates to calves less than 6 months old. These results indicate that the immature bovine testis produces and secretes high levels of ir-inhibin and that the Sertoli cells are a major source of ir-inhibin in prepubertal bull calves.

Age Factors↗

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.

Animals↗

Immunohistochemical detection of inhibin-alpha, -betaB, and -betaA chains and 3beta-hydroxysteroid dehydrogenase in canine testicular tumors and normal testes.

Immunohistochemical detection of inhibin-alpha, -betaA and -betaB chains and 3beta-hydroxysteroid dehydrogenase (HSD) was carried out on primary testicular tumors from 15 dogs and normal testes from three adult dogs. Histopathologically, the tumors were composed of three types: Leydig cell tumors in five dogs, Sertoli cell tumors in five dogs, and seminoma in five dogs. In normal testes, immunostaining against inhibin-alpha, -betaA, and -betaB chains and 3beta-HSD revealed positive reactivity in the cytoplasm of Leydig cells. In testicular tumors, immunoreactive cells against inhibin-alpha, -betaA, and -betaB chains and 3beta-HSD were localized in all Leydig cell tumors but not in any Sertoli cell tumors or seminomas. The results of radioimmunoassay for plasma inhibin in dogs with Leydig cell tumors showed higher concentrations than those in dogs with Sertoli cell tumors and seminomas and those in normal dogs. The concentration of inhibin in the plasma was markedly decreased by the surgical removal of the Leydig cell tumor in one dog. Our findings suggest that inhibin is synthesized by normal and neoplastic Leydig cells in the canine testis, and the secreted inhibin may be inhibin A and inhibin B.

3-Hydroxysteroid Dehydrogenases↗

Superovulation, fertilization and in vitro embryo development in mice after administration of an inhibin-neutralizing antiserum.

The present study was conducted to investigate the effect of immunoneutralization against endogenous inhibin on oocyte and embryo production in adult and immature mice. At 12:00 h on day 2 of oestrus (day 1 of dioestrus), a single i.p. injection of inhibin antiserum (50, 100, 200 or 400 microl per animal) or equine chorionic gonadotrophin (eCG; 10 or 20 iu per animal) or control goat serum (100 microl per animal) was administered to adult female mice. After 48 h, the mice in each of the three groups were given a single i.p. injection of hCG (10 iu per animal). At 42 h after hCG injection, ova were collected from oviducts and cultured in KSOM solution. Treatments with both inhibin antiserum-hCG and eCG-hCG induced superovulation in all the animals tested. The number of oocytes in animals treated with inhibin antiserum was significantly higher (P < 0.05) compared with the control group, and the number of oocytes ovulated in animals treated with 200 or 400 ml inhibin antiserum was significantly (P < 0.05) higher than that in animals treated with 10 or 20 iu eCG. The superovulated oocytes that were fertilized normally in vivo were able to form blastocysts in vitro. The rate of blastocyst development for animals treated with 50-200 ml inhibin antiserum was significantly (P < 0.05) higher than that of the eCG-treated animals. Irrespective of the day of the oestrous cycle, 200 microl inhibin antiserum administered at 12:00 h on each of 4 days induced superovulation in all the animals tested. The rates of oocyte and embryo production by these animals were significantly (P < 0.05) higher than in the control groups. Furthermore, administration of inhibin antiserum at doses of 50, 100, 200 or 400 ml produced similar results in 26-day-old immature mice. These results indicate that passive immunoneutralization of endogenous inhibin alpha-subunit induces superovulation in immature and adult mice. The superovulated oocytes obtained by administration of inhibin antiserum have normal embryonic developmental competence. Thus, it is concluded that this inhibin antiserum method is a new practical alternative for induction of superovulation in mice instead of the more commonly used eCG-hCG protocol.

Animals↗

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.

Adrenocorticotropic Hormone↗

Secretion of inhibin A and inhibin B throughout pregnancy and the early postpartum period in chimpanzees.

Plasma concentrations of inhibin A and inhibin B during pregnancy and early lactation in chimpanzees were determined by enzyme-linked immunosorbent assay (ELISA). Plasma samples were taken from five pregnant chimpanzees at 6-9, 10, 20 and 25 weeks of pregnancy, and following parturition. Throughout pregnancy and the early postpartum period, circulating inhibin A and inhibin B concentrations remained low, at similar levels to those during the normal menstrual cycle in chimpanzees. Concentrations of inhibin A in the placental homogenate were high enough to be measured by the ELISA and by bioassay, whereas circulating inhibin bioactivities in late pregnancy were too low to be measured. Plasma concentrations of FSH remained low with no significant changes throughout pregnancy and the postpartum period. Plasma concentrations of oestradiol-17beta and progesterone at 25 weeks of pregnancy were much higher than normal menstrual cycle levels. It was concluded that in chimpanzees the levels of circulating inhibin A and inhibin B remained low throughout pregnancy and the early postpartum period, and that the concentrations of bioactive dimeric inhibin did not increase towards the end of pregnancy. The suppression of circulating FSH levels during pregnancy is suggested to be controlled by steroid hormones that increased significantly in late pregnancy, and the present findings further suggest that the secretory pattern and role of inhibin during pregnancy in chimpanzees may be different from that in human and other primates.

Animals↗

Effect of hyperprolactinemia induced by pituitary grafts or castration on porphyrin content of the mouse Harderian gland.

The histology and porphyrin concentrations of Harderian glands and plasma prolactin levels were examined in B6C3F1 mice castrated or isografted with pituitaries in combination with the administration of bromocriptine (2-bromo-á-ergocryptine), a potent suppressor of prolactin. Four pituitaries were transplanted underneath the bilateral kidney capsules of each mouse. Furthermore, we investigated Harderian porphyrins and plasma testosterone levels in mice that were castrated or treated with neuroleptic butyrophenone (timiperone), a potent accelerator of prolactin, and treated concurrently with bromocriptine. Light microscopically, pituitary grafts increased the concretion of porphyrin pigments within the Harderian gland lumina. Pituitary grafts or castration increased both Harderian porphyrin concentrations and plasma prolactin levels compared with the intact control mice. In pituitary-grafted or castrated mice, bromocriptine distinctly prevented the rise in both porphyrins and prolactin levels. Administration of butyrophenone did not result in any marked change in testosterone levels, although Harderian gland porphyrins were significantly increased. The present results indicate that in mice prolactin stimulates the porphyrin production of the Harderian gland and has an important role in the regulation of Harderian gland porphyrins.

Animals↗

Irreversible effects of neonatal exposure to p-tert-octylphenol on the reproductive tract in female rats.

It has been known for many years that administration of androgens or estrogens at critical periods of development in mammals causes severe long-term effects on the endocrine/genital systems. The environmental pollutant p-tert-octylphenol (OP) possesses a weak but clear estrogen agonist activity in in vitro and in vivo studies. In the present study, effects of neonatal exposure to OP on the reproductive tract of female rats were investigated. Newborn female pups were injected with 100 mg/kg OP subcutaneously within 24 h after birth. Administration was repeated every other day until postnatal day 15 (total of eight doses). Before weaning, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) remained at low levels during OP exposure, although the serum FSH peak and the high LH level were obvious in the controls. Histologically, inhibition of uterine gland genesis was apparent. The day of vaginal opening was about 4 days earlier in OP-treated animals than in controls. Persistent estrus was consistently observed in OP-treated animals. Atrophic and polycystic ovaries without corpora lutea showed anovulation. In the endometrium, cell-proliferative activity and cell-death were increased and decreased, respectively, and expression of estrogen receptor alpha mRNA was apparent by in situ hybridization. Unexpectedly, endometrial hyperplasias appeared at 8 weeks of age. After ovariectomy, vaginal smears immediately became of castration type and the uterus was atrophied. These results suggested that neonatal exposure to a high dose of OP alters developmental hormonal secretion presumably due to a hypothalamo-pituitary-ovarian disorder, with accelerated vaginal opening, subsequent persistent estrus, and uterine endometrial hyperplasia. The changes in the uterus and vagina are ovary-dependent.

Animals↗