RESUMO
Steroidogenic factor 1 (SF-1, Nr5a1, and Ad4bp) is an orphan nuclear receptor required for adrenal and gonad development and endocrine regulation. To extend our understanding of SF-1 function and the mechanisms controlling its expression, a transgenic rescue strategy was employed to locate important transcriptional control regions and to reveal functional roles of the protein. A rat yeast artificial chromosome containing Ftz-F1, the gene encoding SF-1, was used to generate mice with different transgenes that varied in size. Rat SF-1 mRNA expression was assayed to assess each transgene's targeting ability. SF-1-deficient/transgene-positive (SF-1(-/-); tg/+) "rescue" mice were then generated and the animals' developmental and reproductive status was evaluated. The results identified differences in expression patterns and rescue abilities that provided insight into SF-1 transcriptional control and function. Comparing transgene maps and mRNA profiles placed critical transcriptional elements for pituitary and hypothalamic expression to a region 3' to intron 4, whereas examination of rescued mice revealed that an approximately 153-kb region of the Ftz-F1 locus recapitulates most or all activity ascribed to the endogenous allele. A second line of rescued mice was hypomorphic, with males showing defects in androgen-dependent tissues due to abnormal Leydig cell differentiation. Histological analysis of embryonic (e14.5) and adult testes from these mice implicated SF-1 in roles that are distinct in fetal and adult Leydig cells.
Assuntos
Proteínas de Homeodomínio/fisiologia , Células Intersticiais do Testículo/citologia , Receptores Citoplasmáticos e Nucleares/fisiologia , Fatores de Transcrição/fisiologia , Animais , Diferenciação Celular , Cromossomos Artificiais de Levedura/genética , Cromossomos Artificiais de Levedura/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Imuno-Histoquímica , Células Intersticiais do Testículo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Genéticos , Ratos , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Fator Esteroidogênico 1 , Testículo/citologia , Testículo/embriologia , Testículo/crescimento & desenvolvimento , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transgenes/genéticaRESUMO
Thyroid hormones are important for growth and development of many tissues. Altered thyroid hormone status causes testicular abnormalities. For instance, juvenile hypothyroidism/neonatal transient hypothyroidism induces macroorchidism, increases testicular cell number (Sertoli, Leydig, and germ cells) and daily sperm production. Triiodothyronine (T3) receptors have been identified in sperm, developing germ cells, Sertoli, Leydig, and peritubular cells. T3 stimulates Sertoli cell lactate secretion as well as mRNA expression of inhibin-alpha, androgen receptor, IGF-I, and IGFBP-4. It also inhibits Sertoli cell mRNA expression of Müllerian inhibiting substance (MIS), aromatase, estradiol receptor, and androgen binding protein (ABP) and ABP secretion. T3 directly increases Leydig cell LH receptor numbers and mRNA levels of steroidogenic enzymes and steroidogenic acute regulatory protein. It stimulates basal and LH-induced secretion of progesterone, testosterone, and estradiol by Leydig cells. Steroidogenic factor-1 acts as a mediator for T3-induced Leydig cell steroidogenesis. Although the role of T3 on sperm, germ, and peritubular cells has not yet been completely studied, it is clear that T3 directly regulates Sertoli and Leydig cell functions. Further studies are required to elucidate the direct effect of T3 on sperm, germ, and peritubular cells.
Assuntos
Hormônios Esteroides Gonadais/metabolismo , Hormônios Testiculares/metabolismo , Testículo/metabolismo , Tri-Iodotironina/fisiologia , Regulação da Expressão Gênica , Hormônios Esteroides Gonadais/genética , Humanos , Células Intersticiais do Testículo/citologia , Células Intersticiais do Testículo/metabolismo , Masculino , RNA Mensageiro/metabolismo , Células de Sertoli/citologia , Células de Sertoli/metabolismo , Hormônios Testiculares/genética , Testículo/citologiaRESUMO
The effect of neonatal hypothyroidism on spermatogenesis was studied in Wistar rats of different age groups. Hypothyroidism was induced in newborn male rats from day one postpartum up to day 60 postpartum by daily administration of 0.05% methimazole (MMI) to the nursing mothers or directly through drinking water. The animals were killed at days 10, 15, 30, 40, and 60 postpartum, blood plasma was collected, and testes, epididymides, prostates, and seminal vesicles were separated and weighed. Testes were fixed in formalin for histological studies. Plasma testosterone (T), estradiol (E2), and sex hormone binding globulin (SHBG) were measured by radioimmunoassay. Hypothyroidism significantly reduced seminiferous tubule and lumen diameter. Control rats showed active spermatogenesis whereas in hypothyroid rats, the proliferation and differentiation of germ cells were arrested and their number was decreased. Plasma T, E2, and SHBG levels were significantly decreased at all ages for hypothyroid rats. The absolute weight of testes was decreased irrespective of age (except day 10 postpartum), however ventral, dorsolateral prostate, and epididymis weights were decreased at 30, 40, and 60 days postpartum. Coagulating gland weight was decreased in all age groups of hypothyroid rats. Hypothyroid rats of day 40 and 60 postpartum showed a decrease in absolute seminal vesicle weight. Relative testicular weights of hypothyroid rats decreased by postpartum day 15, 30, 40, and 60 whereas the opposite effect was observed by postpartum day 10. Relative organ weights were increased in epididymides (day 15 and 30 postpartum), seminal vesicles (day 30 and 40 postpartum), and dorsolateral prostates (day 15, 30, and 40 postpartum) and decreased in 10 and 60 day old hypothyroid rat. Ventral prostate relative weight was decreased in 40 and 60 day old rats. Th coagulating gland weight was decreased in 10, 15, and 60 days postpartum and an opposite effect was observed in 30 and 40 days hypothyroid rats. The present study clearly indicates that hypothyroidism adversely affects spermatogenesis; it also indicates that thyroid hormones are essential for normal spermatogenesis. Their effect may either be direct or indirect.
Assuntos
Animais Recém-Nascidos , Hipotireoidismo/fisiopatologia , Espermatogênese , Envelhecimento/fisiologia , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Epididimo/patologia , Estradiol/sangue , Hipotireoidismo/patologia , Masculino , Tamanho do Órgão , Próstata/patologia , Ratos , Ratos Wistar , Glândulas Seminais/patologia , Túbulos Seminíferos/patologia , Globulina de Ligação a Hormônio Sexual/análise , Contagem de Espermatozoides , Testículo/patologia , Testosterona/sangueRESUMO
The impact of hyperthyroidism on epididymal glycosidases was studied in albino rats. Hyperthyroidism was induced in Wistar rats aged 30 days by daily injection of T4 (25 microg/100 g body weight/day intramuscularly) for 30 or 60 days; control rats were injected with vehicle (alkaline saline, pH 7.8). One set of hyperthyroid rats was reverted to euthyroid status by withdrawing T4 treatment after 30 days of hyperthyroidism. To asses the direct effect of thyroid hormone on epididymal hexosaminidases, caput, corpus and cauda tissues were stimulated with 25, 50 or 100 ng/mL T3 for 24 h, after an initial culture of 24 h. The activity of beta-glucosidase decreased in caput, corpus and cauda epididymis of hyperthyroid rats. beta-Galactosidase activity increased in the caput epididymis irrespective of the duration of hyperthyroidism. While a similar decrease occurred in the corpus and cauda epididymis in the 30 day hyperthyroid group, an opposite trend was observed in 60 day hyperthyroid rats. Caput beta-N-acetylglucosaminidase activities increased at both time points, whereas activity decreased in the corpus and cauda in 30 day, but increased in 60 day hyperthyroid rats. Hyperthyroidism consistently increased caput and corpus beta-N-acetylgalactosaminidase activity irrespective of the duration. Cauda epididymal beta-N-acetylgalactosaminidase activity was decreased in 30 day and increased in 60 day hyperthyroid rats. Hyperthyroidism induced changes in caput beta-galactosidase, beta-N-acetylgalactosaminidases, corpus beta-N-acetylglucosaminidase and cauda beta-N-acetylgalactosaminidase which were irreversible while the remaining actvities were brought back to normal when T4 treatment was withdrawn. In vitro studies showed that T3 stimulates epididymal hexosaminidases (beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase) irrespective of the dose. These data suggest that thyroid hormones have a specific and direct influence on glycosidases in specific regions of the epididymis.
Assuntos
Epididimo/enzimologia , Hexosaminidases/metabolismo , Hipertireoidismo/enzimologia , beta-Galactosidase/metabolismo , beta-Glucosidase/metabolismo , Animais , Modelos Animais de Doenças , Hormônios/sangue , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar , Espermatozoides/enzimologia , beta-N-Acetil-GalactosaminidaseRESUMO
We have previously demonstrated that neonatal and transient neonatal hypothyroidism modulates Leydig, Sertoli, and germ cell numbers, sex steroids and androgen binding protein concentration. The present study was undertaken to study the effect of neonatal onset hypothyroidism on Leydig and peritubular myoid cell numbers, plasma and testicular interstitial fluid (TIF) sex steroid concentration at different age groups of Wistar rats. Hypothyroidism was induced by giving 0.05% methimazole (MMI) to lactating mothers or directly to the male pups from day 1 postpartum through days 10, 15, 30, 40 and 60 postpartum. To confirm hypothyroidism, plasma thyroid hormones and TSH were assayed. Plasma and TIF testosterone, progesterone, dihydrotestosterone (DHT) and estradiol were assayed by radioimmunoassay. Leydig cell number in hypothyroid rats were less than the age-matched controls. The diameter of Leydig cells in hypothyroid rats was smaller than the controls but 10 days old hypothyroids alone had larger than control rats. A significant decrease of peritubular myoid cell number was observed in 30, 40 and 60 days hypothyroid rats and increased in 10 and 15 days hypothyroidism. Hypothyroid rats had elevated level of plasma LH and decreased GH (except day 10 postpartum). Plasma PRL level was increased in 10 and 15 days hypothyroid rats and an opposite effect was observed in 40 and 60 days hypothyroidism. Plasma testosterone, DHT and estradiol were decreased in all hypothyroid rats. However, plasma progesterone level in hypothyroid rats was significantly higher at days 10, 30, and 40 postpartum and an opposite effect was seen in 15 and 60 days experimental groups. TIF testosterone and progesterone titre showed a consistent decrease in hypothyroid rats irrespective of the duration. In hypothyroid rats, TIF DHT levels decreased significantly in days 10, 40 and 60 postpartum. However, it increased in days 15 and 30 postpartum. Except at day 10 postpartum, the level of TIF estradiol in hypothyroid rats was significantly less than their age matched controls. Our data clearly indicate that neonatal onset hypothyroidism adversely affect Leydig cell proliferation along with impaired steroidogenesis.
Assuntos
Animais Recém-Nascidos , Hormônios Esteroides Gonadais/sangue , Hipotireoidismo/sangue , Hipotireoidismo/patologia , Células Intersticiais do Testículo/patologia , Testículo/metabolismo , Envelhecimento , Animais , Contagem de Células , Di-Hidrotestosterona/análise , Di-Hidrotestosterona/sangue , Estradiol/análise , Estradiol/sangue , Espaço Extracelular/química , Hormônios Esteroides Gonadais/análise , Hormônio do Crescimento/sangue , Hormônio Luteinizante/sangue , Masculino , Progesterona/análise , Progesterona/sangue , Prolactina/sangue , Ratos , Ratos Wistar , Testosterona/análise , Testosterona/sangueRESUMO
Ventral prostatectomy decreased serum thyroid hormones and histology of the thyroid gland indicate that hypothyroid condition. Co-culture of thyroid gland and ventral prostate stimulates thyroid hormone secretion. In the present study we report prostatic thyrotropin releasing hormone (TRH) is the stimulating factor of thyroid hormone secretion. Mature rat (90 days old) ventral prostate, anterior pituitary and thyroid glands were co-cultured in vitro with or without TRH antibody to assess the direct influence ofprostatic TRH on thyroid hormone secretion. Total thyroxine (T4) and triiodothyronine (T3) were increased significantly in the culture media of ventral prostate, anterior pituitary and thyroid gland when compared with thyroid gland plus anterior pituitary culture media. However, media T4 and T3 concentration decreased significantly in thyroid gland alone; also in thyroid gland plus ventral prostate, thyroid gland plus anterior pituitary and thyroid gland plus anterior pituitary plus ventral prostate were co-cultured with TRH antibody (Ab) in a dose dependent manner. The results suggest that ventral prostatic TRH is one ofthe stimulating factors of thyroid hormone secretion under these in vitro conditions.
Assuntos
Próstata/fisiologia , Glândula Tireoide/fisiologia , Hormônios Tireóideos/metabolismo , Hormônio Liberador de Tireotropina/farmacologia , Animais , Anticorpos/farmacologia , Técnicas de Cocultura , Meios de Cultivo Condicionados , Masculino , Adeno-Hipófise/fisiologia , Ratos , Ratos Wistar , Hormônio Liberador de Tireotropina/imunologia , Tiroxina/metabolismo , Tri-Iodotironina/metabolismoRESUMO
The impact of progesterone on serum hormonal profiles in the presence and absence of gonads was studied in adult male and female albino rats. Progesterone was administered intramuscularly for 30 days at a dose of 1 mg/100g body weight/day. Serum testosterone, estradiol and prolactin titres decreased in male and female rats with intact gonads given progesterone. While the levels of both luteinizing hormone (LH) and follicle stimulating hormone (FSH) decreased in male rats with intact gonads, only FSH decreased in female rats. The inhibitory effect of progesterone on serum estradiol, LH, FSH and prolactin persisted even after gonadectomy in male rats. This persistent inhibitory effect of progesterone was also seen on serum testosterone, FSH and prolactin levels of female rats. Ovariectomy modified progesterone action on LH, as is evident from the decreased levels of LH observed only in ovariectomized rats given progesterone. While progesterone had no effect on serum T3 and T4 in male rats, gonadectomy altered the levels of T3 and T4 in male and female rats. Progesterone increased the levels of T3 and decreased the levels of T4 in ovariectomized rats. Growth hormone (GH) and thyroid stimulating hormone (TSH) levels seem to be resistant to changes in progesterone titre, irrespective of the sex and gonadal status. The present data suggest the existence of a sex specific effect of progesterone on gonadotrophins. The data on T3, T4 and TSH reveals that progesterone has no effect on the pituitary thyroid axis in the presence of gonads.
Assuntos
Hormônios/sangue , Progesterona/farmacologia , Animais , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Masculino , Orquiectomia , Ovariectomia , Progesterona/administração & dosagem , Prolactina/sangue , Ratos , Caracteres Sexuais , Testosterona/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
The effect of rat prolactin (rPRL) on basal and LH-, GH- and T3-mediated testosterone and oestradiol secretion was studied in pubertal rat Leydig cells. Purified Leydig cells were cultured for 24 h at 37 degrees C in a medium containing 4% foetal calf serum (FCS). The medium was then replaced with fresh medium containing different concentrations of rPRL (5-400 ng/mL) for 48 h at 34 degrees C without FCS. rPRL increased testosterone secretion by Leydig cells at doses of 50-400 ng and maximum stimulation was observed at a dose of 200 ng. Oestradiol secretion was parallel to that of testosterone except at low doses (5-50 ng/mL). To assess the modulatory effect of rPRL on LH-, GH- and T3-induced Leydig cell testosterone and oestradiol secretion, minimum (50 ng) and maximum (200 ng) effective doses of rPRL were co-administered with LH (25/100 ng), GH (10/50 ng) and T3 (25/50 ng). Co-administration of rPRL (50/100 ng) with T3 (25/50 ng) decreased testosterone secretion. While co-administration of T3 (25 ng) decreased rPRL-induced oestradiol secretion, the latter was unaltered at a dose of 50 ng T3. A minimum effective dose of rPRL (50 ng) plus LH (25 ng) stimulated both testosterone and oestradiol secretion. While a maximum effective dose of rPRL (200 ng) did not alter LH (25 ng)-induced testosterone and oestradiol secretion, it inhibited testosterone secretion induced by 100 ng LH and increased oestradiol secretion. Both doses of rPRL (50, 200 ng) plus GH (10/50 ng) inhibited testosterone secretion when compared with testosterone secretion induced by either GH or PRL alone and stimulated oestradiol secretion. The present in vitro study indicates that rPRL stimulates both testosterone and oestradiol secretion by Leydig cells and that this effect can be modulated by LH, GH and T3.
Assuntos
Estradiol/metabolismo , Células Intersticiais do Testículo/metabolismo , Prolactina/metabolismo , Testosterona/metabolismo , Animais , Células Cultivadas , Hormônio do Crescimento Humano/metabolismo , Hormônio Luteinizante/metabolismo , Masculino , Ratos , Ratos Wistar , Tri-Iodotironina/metabolismoRESUMO
The effect of T3 on basal and LH mediated synthesis and secretion of testosterone and oestradiol by puberal rat Leydig cells was studied in vitro. Percoll gradient purified Leydig cells (1 x 10(3)) were cultured for 48 hours at 34 degrees C in a medium containing a range of 5-400 ng/mL concentration of T3 or ovine LH after 24 hours initial culture at 37 degrees C. T3 increased testosterone and oestradiol secretions in a dose dependent manner which reached the saturation point with 50 ng dose. While the minimum effective dose of T3 (25 ng) potentiated the stimulatory effect of the minimum effective dose of LH (25 ng) on testosterone secretion, it suppressed the effect of the saturation dose of LH (100 ng). Fifty ng T3 quelled the stimulatory effect of either dose of LH. Both doses of T3 increased oestradiol secretion, irrespective of the dose of LH. Addition of androstenedione (500 ng/mL) to the culture medium enhanced 25 ng T3 induced testosterone and oestradiol secretions. While androstenedione potentiated the stimulatory effect of T3 (25 ng) on LH (25 ng) induced testosterone and oestradiol secretions, it reversed the inhibitory effect of 50 ng T3 on LH mediated testosterone secretion which was accompanied by a decrease in oestradiol secretion. Puromycin (35 microg/mL) suppressed the stimulatory effect of T3 on basal and LH mediated testosterone and oestradiol production. Taken together, the present results indicate a direct stimulatory effects of T3 on basal production of testosterone and oestradiol by Leydig cells and its modulatory effect on LH mediated steroidogenic activity varies depending upon the intensity of LH stimuli.
Assuntos
Estradiol/metabolismo , Células Intersticiais do Testículo/metabolismo , Hormônio Luteinizante/farmacologia , Testosterona/metabolismo , Tri-Iodotironina/farmacologia , Androstenodiona/metabolismo , Animais , Interações Medicamentosas , Células Intersticiais do Testículo/efeitos dos fármacos , Masculino , Puromicina/farmacologia , Ratos , Ratos WistarRESUMO
The stimulatory and inhibitory effects on testicular steroidogenesis of transient neonatal hypothyroidism from day 1 postpartum through different postnatal developmental events on testis at puberal age (60 days old) were studied in vivo. Hypothyroidism was induced in neonates by feeding the lactating mother or directly with 0.05% methimazole (MMI) through drinking water from the day of parturition to 10, 15, 30, 40 and 60 days, and were killed at day 60 postpartum. Plasma and testicular interstitial fluid (TIF) progesterone, testosterone, dihydrotestosterone (DHT) and estradiol concentrations were assessed. Testis weight and volume significantly increased in rats subjected to 10 and 15 days of hypothyroidism, decreased in rats subjected to 30, 40 and 60 days of hypothyroidism. A consistent increase in Leydig cell number was seen in puberal rats subjected to transient neonatal hypothyroidism but decreased in 60 days hypothyroid rats. Peritubular myoid cell number was consistently decreased in all experimental rats. Leydig cell diameter decreased consistently in all experimental groups. Persistent hypothyroidism (60 days hypothyroid) consistently decreased both plasma and TIF sex steroids. In transient hypothyroid rats, progesterone concentration decreased in both plasma and TIF. Transient hypothyroidism from birth to day 10 postnatal age maintained normal titre of plasma testosterone, whereas a significant increase in TIF testosterone concentration was evident when compared with controls. All other groups of rats subjected to transient neonatal hypothyroidism had consistently low titres of plasma and TIF testosterone. Plasma DHT concentrations in rats subjected to transient neonatal hypothyroidism remained unaltered. However, TIF DHT increased in 10 days
Assuntos
Animais Recém-Nascidos , Hormônios Esteroides Gonadais/sangue , Hormônios Esteroides Gonadais/metabolismo , Hipotireoidismo/metabolismo , Maturidade Sexual , Testículo/metabolismo , Animais , Contagem de Células , Di-Hidrotestosterona/sangue , Estradiol/sangue , Hipotireoidismo/sangue , Hipotireoidismo/patologia , Células Intersticiais do Testículo , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão , Progesterona/sangue , Ratos , Testículo/patologia , Testosterona/sangue , Tireotropina/sangue , Tiroxina/sangue , Fatores de Tempo , Tri-Iodotironina/sangueRESUMO
The modulatory effect of GH on basal, LH and T3 mediated secretion of testosterone and oestradiol by purified rat (60 day old) Leydig cells was studied in vitro. Percoll gradient purified Leydig cells (1 x 10(3)) were cultured for 48 hours at 34 degrees C in a medium containing different concentrations of rat GH (5-400 ng/mL), after an initial culture for 24 hours at 37 degrees C. GH increased testosterone and oestradiol secretions in a dose dependent manner. While testosterone secretion reached the saturation point with 50 ng GH, oestradiol secretion reached the saturation point with 150 ng GH, followed by diminished secretions. Co-administration of minimum (10 ng) effective does of GH with minimum (25 ng) or maximum (100 ng) effective doses of oLH significantly decreased the testosterone secretion. However, an increased secretion of testosterone was observed when maximum effective doses of rGH (50 ng) and oLH (100 ng) were co-administered. Minimum effective (25 ng) or maximum effective (50 ng) doses of T3 inhibited GH mediated secretion of testosterone in vitro. Oestradiol concentration in the culture medium increased when either dose of rGH was co-administered with the minimum or maximum effective doses of oLH. T3 50 ng augmented the secretion of oestradiol by Leydig cells in the presence of GH. These results indicate that GH acts as a gonadotrophin to stimulate testosterone and oestradiol secretions by Leydig cells, and that it modulates LH or T3 induced secretion of these steroids, depending on the intensity of their stimulation.
Assuntos
Estradiol/metabolismo , Hormônio do Crescimento Humano/farmacologia , Células Intersticiais do Testículo/fisiologia , Hormônio Luteinizante/farmacologia , Testosterona/metabolismo , Tri-Iodotironina/farmacologia , Animais , Masculino , Ratos , Ratos Wistar , OvinosRESUMO
Earlier studies have shown that thyroid hormones play an important role in glycoprotein metabolism in the prostate. In this paper, hypothyroidism induced changes in prostatic glycoprotein-associated monosaccharides and fructose concentrations were studied in 30-day-old peripubertal rats. Hypothyroidism was induced by total surgical thyroidectomy and confirmed by radioimmunoassay (RIA) of thyroid hormones and thyroid stimulating hormone (TSH). Animals were killed after 30 and 60 days post-thyroidectomy. To test the direct effect of thyroid hormones on prostatic monosaccharides, prostatic tissue was incubated for 24 h at 37 degrees C with 25, 50 or 100 ng/mL T3. Ventral prostatic hexosamines and sialic acid concentrations were significantly decreased in hypothyroid rats aged 30 and 60 days, whereas fucose concentration was increased at 30 days but decreased at 60 days in hypothyroid rats. In the case of the dorsolateral prostate, hypothyroidism enhanced the concentration of hexosamines but caused a decrease in levels of fucose, sialic acid and fructose, irrespective of the duration of hypothyroidism. Concentrations of fucose, fructose and hexosamines in the anterior prostate were decreased and sialic acid concentration was increased in 60-day hypothyroid rats. In in vitro studies, the concentrations of fucose, sialic acid and hexosamines were significantly increased in all three prostatic lobes irrespective of the T3 dose with which they had been incubated. A consistent increase in fructose concentration was observed in anterior and dorsolateral prostates when incubated with different doses of T3 stimulation. It is concluded that the influence of hypothyroidism on prostatic monosaccharides seems to be specific for each sugar in different lobes of the prostate. These results clearly show that thyroid hormones differentially regulate prostatic glycoprotein metabolism.
Assuntos
Monossacarídeos/metabolismo , Próstata/metabolismo , Tireoidectomia , Animais , Estrogênios/sangue , Masculino , Ratos , Ratos Wistar , Testosterona/sangue , Hormônios Tireóideos/sangueRESUMO
The effects of excess corticosterone on luteinizing hormone (LH)-stimulated Leydig cell testosterone production and activity of 11beta-HSD was studied. Adult male rats (200-250 g body weight) were treated with corticosterone-21-acetate (2 mg/100 g body weight, i.m., twice daily) for 15 days. Another set of rats was treated with corticosterone (dose as above) plus LH (ovine LH 100 microg/kg body weight, s.c., daily) for 15 days. Corticosterone administration significantly increased serum and testicular interstitial fluid (TIF) corticosterone but decreased testosterone levels. Administration of LH with corticosterone partially prevented the decrease in serum and TIF testosterone. The oxidative activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) was significantly decreased in Leydig cells of rats treated with corticosterone alone and in combination with LH. The direct effect of corticosterone on Leydig cell steroidogenic potency was also studied in vitro. Addition of corticosterone to Leydig cell culture showed a dose dependent effect on LH-stimulated testosterone production. Corticosterone at 50 and 100 ng/ml did not alter LH-stimulated testosterone production, but at high doses (200-400 ng/ml), decreased basal and LH-stimulated testosterone production. Basal and LH-stimulated cAMP production was not altered by corticosterone in vitro. It is concluded from the present study that elevated levels of corticosterone decreased the oxidative activity of 11beta-HSD and thus resulting in impaired Leydig cell steroidogenesis and the inhibitory effects of corticosterone on testosterone production appear to be mediated through inhibition of LH signal transduction at post-cAMP level.
Assuntos
Corticosterona/farmacologia , Hidroxiesteroide Desidrogenases/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/enzimologia , Hormônio Luteinizante/farmacologia , Testosterona/biossíntese , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1 , Animais , Células Cultivadas , Corticosterona/sangue , AMP Cíclico/metabolismo , Ativação Enzimática/efeitos dos fármacos , Espaço Extracelular/metabolismo , Técnicas In Vitro , Células Intersticiais do Testículo/citologia , Masculino , Ratos , Ratos WistarRESUMO
The mechanism involved in the inhibitory actions of chronic corticosterone treatment on Leydig cell steroidogenesis was studied in adult Wistar rats. Rats were treated with corticosterone-21-acetate (2 mg/100 g body weight, i.m., twice daily) for 15 days and another set of rats was treated with corticosterone plus ovine luteinizing hormone (oLH) (100 microg/kg body weight, s.c., daily) for 15 days. Chronic treatment with corticosterone increased serum corticosterone but decreased serum LH, testosterone, estradiol and testicular interstitial fluid (TIF) testosterone and estradiol concentrations. Administration of LH with corticosterone partially prevented the decrease in serum and TIF testosterone and estradiol. Leydig cell LH receptor number, basal and LH-stimulated cAMP production were diminished by corticosterone treatment which remained at control level in the corticosterone plus LH treated rats. Activities of steroidogenic enzymes, 3beta- and 17beta-hydroxysteroid dehydrogenase (3beta-HSD and 17beta-HSD) were significantly decreased in corticosterone treated rats. LH plus corticosterone treatment did not affect 3beta-HSD activity but decreased 17beta-HSD activity, indicating a direct inhibitory effect of excess corticosterone on Leydig cell testosterone synthesis. The indirect effect of corticosterone, thus, assume to be mediated through lower LH which regulates the activity of 3beta-HSD. Basal, LH and cAMP-stimulated testosterone production by Leydig cells of corticosterone and corticosterone plus LH treated rats were decreased compared to control suggesting the deleterious effect of excess corticosterone on LH signal transduction and thus steroidogenesis.
Assuntos
Corticosterona/análogos & derivados , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Hormônio Luteinizante/metabolismo , Esteroides/biossíntese , Animais , Corticosterona/administração & dosagem , Corticosterona/sangue , Corticosterona/farmacologia , AMP Cíclico/biossíntese , Estradiol/biossíntese , Estradiol/sangue , Técnicas In Vitro , Hormônio Luteinizante/sangue , Hormônio Luteinizante/farmacologia , Masculino , Ratos , Ratos Wistar , Receptores do LH/efeitos dos fármacos , Receptores do LH/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esteroides/sangue , Testosterona/biossíntese , Testosterona/sangueRESUMO
The impact of neonatal onset hypothyroidism from day 1 postpartum through different postnatal developmental events on rat testis was studied in vivo. Hypothyroidism was induced in neonates by feeding the lactating mother or directly with 0.05% methimazole (MMI) through drinking water from the day of birth and were killed at day 10, 15, 30, 40 and 60 postpartum. Hypothyroidism was confirmed by radioimmunoassay of thyroid hormones and TSH. Sertoli cell number, plasma and testicular interstitial fluid (TIF) androgen binding protein (ABP) concentration was quantified. Sertoli cell number was consistently decreased in all hypothyroid rats. Plasma ABP was also decreased irrespective of the duration of hypothyroidism. Unlike plasma ABP, TIF ABP concentration in hypothyroid rats increased at day 10, and 15 postpartum and decreased in other age groups. Plasma FSH level was increased significantly in all hypothyroid groups. The present investigation points out that suppression of T3 during the critical period of Sertoli cell proliferation affects their number and functional activity.
Assuntos
Proteína de Ligação a Androgênios/metabolismo , Animais Recém-Nascidos , Hipotireoidismo/metabolismo , Hipotireoidismo/patologia , Células de Sertoli/patologia , Testículo/metabolismo , Envelhecimento , Proteína de Ligação a Androgênios/sangue , Animais , Contagem de Células , Espaço Extracelular/metabolismo , Hormônio Foliculoestimulante/sangue , Hipotireoidismo/induzido quimicamente , Masculino , Metimazol , Tamanho do Órgão , Ratos , Testículo/patologia , Tireotropina/sangueRESUMO
The impact of transient neonatal hypothyroidism on growth and function of puberal testis during different milestones of postnatal testicular development was studied in Wistar rats. Rat pups were made hypothyroid for 10, 15, 30, 40 and 60 days of postnatal age from birth by providing 0.05% (W/V) methimazole (MMI) in the drinking water of the mother, from day 1 postpartum till weaning (25 days postpartum) and thereafter in the drinking water. Control rats were raised without MMI treatment. Sertoli cell number and its function was assessed on day 60 postpartum. Sertoli cell number increased consistently in 10, 15, 30 and 40 days transient hypothyroid rats but decreased in rats subjected to continuous hypothyroidism from birth to 60 days postpartum. Rats subjected to continuous hypothyroidism from birth showed spermatogenic arrest at puberty and had only a single layer of spermatogonia. Transient neonatal hypothyroidism for 10 (or) 15 days from birth increased spermatocytes (pachytene and zygotene), spermatids (elongated and round) whereas, that of 30 and 40 days decreases the number of germ cells. Plasma androgen binding protein (ABP) concentration decreased in puberal rats belonging to all groups, whereas the testicular interstitial fluid (TIF) concentration of ABP increased significantly in 10 and 15 days hypothyroid rats while it decreased in all other groups. These findings indicate that the mitogenic activity of Sertoli cell is increased irrespective of the duration of transient neonatal hypothyroidism. However, the functional activity of Sertoli cells (ABP production) in these puberal rats varies depending upon the postnatal period at which the animals were in hypothyroid state.
Assuntos
Proteína de Ligação a Androgênios/metabolismo , Animais Recém-Nascidos , Hipotireoidismo/patologia , Células de Sertoli/patologia , Contagem de Espermatozoides , Testículo/metabolismo , Envelhecimento , Proteína de Ligação a Androgênios/sangue , Animais , Contagem de Células , Espaço Extracelular/metabolismo , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/metabolismo , Masculino , Metimazol , Tamanho do Órgão , Ratos , Ratos Wistar , Túbulos Seminíferos/patologia , Espermátides , Espermatócitos , Testículo/patologia , Hormônios Tireóideos/sangue , Fatores de TempoRESUMO
BACKGROUND: Endocrine cells of the prostate secrete thyrotropin (TSH)-releasing hormone (TRH), TRH- and TSH-like peptides, and growth factors. Propylthiouracil- and methimazole-induced hypothyroidism increased prostatic levels of TRH in rats as in hypothalamus, whereas thyroxine (T4) replacement decreased TRH. From these reports, we inferred the existence of a prostate-thyroid axis. METHODS: The influence of the prostate on the thyroid gland was studied in albino rats. Ventral prostate was surgically removed on day 31 postpartum. The animals were sacrificed on day 60 postoperation. Serum thyroid hormones were assayed by radioimmunoassay (RIA). For in vitro studies, normal thyroid and ventral prostate glands were cocultured with or without thyroid-stimulating hormone (TSH) antibody, to assess the direct influence of prostatic secretions on thyroid hormone secretion. RESULTS: Serum total and free T4 and triiodothyronine (T3) were significantly reduced in ventral prostatectomized rats. Histological analysis of the thyroid showed that the diameters of the peripheral and middle follicles, colloid epithelial cells, and nuclei were increased in prostatectomized rats, indicating hypothyroid status. Total T3 and T4 were significantly elevated in the culture medium when thyroid and prostate were cocultured, irrespective of the presence of TSH antibody. CONCLUSIONS: The present study suggests that ventral prostatic secretions have a stimulatory role on the thyroid gland.
Assuntos
Próstata/fisiologia , Glândula Tireoide/fisiologia , Hormônios Tireóideos/metabolismo , Envelhecimento/fisiologia , Animais , Masculino , Próstata/metabolismo , Prostatectomia , Radioimunoensaio , Ratos , Ratos Wistar , Sensibilidade e Especificidade , Estimulação QuímicaRESUMO
The impact of hyper- and hypothyroidism on prostatic glycosidases was investigated. Hyper-thyroidism was induced by administering L-thyroxine (25 micrograms/100 g body weight/day) for 60 days and hypothyroidism was induced by total thyroidectomy. To test the direct influence of thyroid hormones, prostatic lobes were incubated with different concentrations (10, 25 and 50 ng/mL) of T3 and beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase were assayed. Serum levels of thyroid hormones, oestradiol and testosterone increased in hyperthyroid, and decreased in hypothyroid rats. TSH decreased in hyperthyroid, and an opposite trend was seen in thyroidectomized, rats. Prostatic [anterior (coagulating glands), dorsolateral and ventral prostates] beta-glucosidase, beta-galactosidase, beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase activities increased uniformly in hyperthyroid, and decreased in thyroidectomized, rats. In vitro studies showed a dose-dependent stimulatory effect of T3 on beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase in all three lobes of the prostate. From the present study, it is concluded that hyperthyroidism augments and hypothyroidism inhibits prostatic glycosidases and T3 has a direct stimulatory effect on these enzymes.
Assuntos
Glicosídeo Hidrolases/metabolismo , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Próstata/enzimologia , Hormônios Tireóideos/metabolismo , Animais , Peso Corporal , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar , Tireoidectomia , TiroxinaRESUMO
IgG comprises of four subclasses which differ from each other with respect to their biological properties. Fc gamma receptor shedding as well as a variety of T cell cytokines are influential in the distribution of these subclasses, but the route the antigen is introduced into the body is also important. With regard to nonorgan-specific autoimmune conditions, such as rheumatoid arthritis and systemic lupus erythematosus, IgG1 and IgG3 autoantibodies predominate, whereas IgG4 antibodies are regularly encountered in organ-specific autoimmune diseases. This suggests that the target organ may be continuously stimulating the immune system.