Biomedical subjects

R R Maran

Publications and source records attributed to R R Maran.

10 recordsLinked to original sources

PubMed2001

Prolactin and Leydig cells: biphasic effects of prolactin on LH-, T3- and GH-induced testosterone/oestradiol secretion by Leydig cells in pubertal rats.

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.

Animals↗

PubMed2000

Chronic administration of corticosterone impairs LH signal transduction and steroidogenesis in rat Leydig cells.

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.

Animals↗

PubMed2000

Thyroidectomy modulates rat prostatic monosaccharides.

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.

Animals↗

PubMed2000

Chronic corticosterone treatment impairs Leydig cell 11beta-hydroxysteroid dehydrogenase activity and LH-stimulated testosterone production.

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.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

PubMed2000

T3 directly stimulates basal and modulates LH induced testosterone and oestradiol production by rat Leydig cells in vitro.

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.

Androstenedione↗

PubMed2000

Transient neonatal hypothyroidism alters plasma and testicular sex steroid concentration in puberal rats.

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

Animals↗

PubMed1998

Impact of altered thyroid hormone status on prostatic glycosidases.

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.

Animals↗

PubMed1995

Inhibition of Leydig cell activity in vivo and in vitro in hypothyroid rats.

Leydig cell steroidogenic activity under basal and stimulated conditions was studied in hypothyroid rats. Hypothyroidism was induced at a prepubertal age (30 days postpartum) by surgical thyroidectomy, and L-thyroxine (T4) supplementation (6 micrograms/100 g body weight/day for 30 days) to hypothyroid rats was begun after 30 days. Hypothyroidism for 60 days reduced serum LH and FSH without affecting prolactin. Serum and intratesticular testosterone and the specific activity of Leydig cell 3 beta- and 17 beta-hydroxysteroid dehydrogenases diminished in hypothyroid rats. The stimulatory effect of LH on Leydig cell steroidogenic activity and cAMP was also adversely affected in hypothyroid rats. All these changes were reversed by T4 supplementation. The present results suggest that prepubertal hypothyroidism suppresses both basal and stimulated Leydig cell activity in adult rats.

17-Hydroxysteroid Dehydrogenases↗

PubMedDate not supplied

Impact of neonatal onset hypothyroidism on Sertoli cell number, plasma and testicular interstitial fluid androgen binding protein concentration.

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.

Aging↗

PubMedDate not supplied

Duration-dependent effect of transient neonatal hypothyroidism on sertoli and germ cell number, and plasma and testicular interstitial fluid androgen binding protein concentration.

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.

Aging↗