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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain sexual differentiation occurs during the steroid-sensitive phases in early development, and is affected particularly by exposure to oestrogens formed in the brain by aromatisation of androgen. The organisational effects of oestrogen result in male-specific neuronal morphology, control of reproductive behaviour, and patterns of gonadotrophin secretion. A question which still has to be resolved is what determines changes in aromatase activity effective for the differentiation of sexually dimorphic brain development during sensitive periods of growth. In the mouse, a sex difference exists at early stages of embryonic development in aromatase-containing neurones of the hypothalamus. The embryonic aromatase system is regulated later in foetal development by androgens. Testosterone treatment increases the numbers of aromatase-immunoreactive hypothalamic neuronal cell bodies. Kinetic evidence from studies on the avian brain suggest that endogenous steroid inhibitors of aromatase, probably formed within neuroglia, also have a role in the control of oestrogen production. Inhibitory kinetic constant determination of endogenous androgenic metabolites formed in the brain showed that preoptic aromatase is potently inhibited by 5 alpha-androstanedione(K(i)=6nM) and less strongly by 5 beta-dihydrotestosterone (K(i)=350nM). Regulation by steroidal and possibly non-steroidal inhibitors may contribute to the special characteristics and plasticity in aromatase activity which develops at certain stages in ontogeny.
J Steroid Biochem Mol Biol 1996 Jan
PMID:Regulation of sex-specific formation of oestrogen in brain development: endogenous inhibitors of aromatase. 860 41

Androgen production by adult rat Leydig cells is stimulated by pituitary LH but can also be modulated in vitro by paracrine stimulatory and inhibitory factors, many of which belong to growth factor families. Their actions are mediated through cell surface or extracellular matrix proteoglycans and the aim of this study was to determine the role of cell surface heparan sulfate proteoglycans in the regulation of testosterone secretion by adult rat Leydig cells. The presence of sodium chlorate (25 mM) and protamine sulfate (10 micrograms/ml) inhibited testosterone production by LH stimulated cells by over 50%, but had no effect on unstimulated cells. The LH responsiveness and testosterone production returned to normal after these agents were removed from the culture media. No significant difference in LH receptor numbers at the end of the culture period was seen between sodium chlorate treated and untreated cells. Testosterone production by dibutryl-cAMP stimulated Leydig cells was also inhibited by sodium chlorate. The addition of heparin inhibited testosterone production by LH stimulated cells in a dose-dependent manner, however, in unstimulated Leydig cells heparin stimulated testosterone production to up to 50% of that seen in LH stimulated cells. These data suggest that cell surface heparan sulfate proteoglycans modulate testosterone production by adult Leydig cells in vitro, and that this may involve the autocrine actions of heparin binding growth factors on the Leydig cells.
Mol Cell Endocrinol 1996 Apr 19
PMID:Evidence that heparin binding autocrine factors modulate testosterone production by the adult rat Leydig cell. 873 91

The effect of testosterone on the morphology and biochemistry of adult castrated rat liver is described. Castration decreases mean weight and volume of hepatocytes, volume and surface area of sinusoidal lumen, and apparently increases cell number per g of tissue. These variations indicate cell distress. Testosterone administration restored sinusoidal volume and surface area, indicating a true hyperplastic response and improved trophic conditions. Acid soluble nucleotides, RNA and DNA content were lower after castration, being partially restored after testosterone treatment. This restoration, however, was only statistically significant for total guanylate. We concluded that testosterone deficiency and administration exerts a specific effect on the liver in terms of morphological and biochemical changes. Purine nucleotide metabolism is probably the first target of hormonal action, since its changes are the most significant and useful to explain all the other observations.
Mol Cell Endocrinol 1996 May 31
PMID:Effect of testosterone on purine metabolism and morphometric parameters in the rat liver. 880 31

Of the three ubiquitously expressed transforming growth factor-beta (TGF beta) receptors, only type I and type II receptors contain serine/threonine kinase activity and have a direct role in TGF beta signal transduction. In the prostate, it has been reported that the level of type III receptor expression increases transiently after castration. However, the relationship between the TGF beta signaling receptors, type I and type II, and androgen is currently unclear. Thus, in the present study, we made an initial attempt to elucidate the effect of androgen on type I and type II receptor expression in the rat ventral prostate by measuring the levels of messenger RNA (mRNA) and protein at specific time points after castration up to 10 days. Within 3 days after castration, an increase in type II receptor mRNA was observed in the prostate, and the level continued to rise until 7 days postcastration (approximately 8-fold increase). Between days 7-10 postcastration, no significant change in the level of type II receptor mRNA was observed. Testosterone administration immediately after castration abolished the induction of type II receptor mRNA during the same 10-day period. Western blot analysis performed for type II receptor showed a similar result, in that the level of type II receptor protein increased approximately 5-fold by day 10 postcastration. In a similar manner to the expression of type II receptor mRNA, the level of type I receptor mRNA increased steadily until day 7 postcastration (approximately 6-fold increase). Between days 7-10 postcastration, the level of type I receptor mRNA did not change significantly. As with type II receptor mRNA, the induction of type I receptor mRNA was suppressed when testosterone was administered immediately after castration. To localize the expression of TGF beta receptor type II, immunohistochemical studies were performed. The results of these studies demonstrated a preferential localization of type II receptor in the prostatic epithelial cells and an increased staining intensity for the receptor after castration. Taken together, these data indicate that TGF beta signaling receptors, type I and type II, are under negative androgenic regulation at the transcriptional level and that TGF beta may be an important regulator of a stromal-epithelial interaction in the rat ventral prostate.
Mol Endocrinol 1996 Jan
PMID:Expression and localization of transforming growth factor-beta receptors type I and type II in the rat ventral prostate during regression. 883 50

Recently we have demonstrated that melatonin secretion is increased in untreated male patients with GnRH deficiency. Testosterone administration to these patients decreased melatonin secretion to normal levels. These data, however, did not exclude a gonadotropic effect on melatonin secretion. To further elucidate whether gonadal steroids and/or gonadotropins modulate melatonin secretion in humans we compared untreated young males with hypogonadotropic hypogonadism (IGD, n = 6), and hypergonadotropic hypogonadism caused by KlinEfelter's syndrome (KS, n = 11) to normal pubertal male controls (n = 7). KS patients were subdivided into two groups: KS-1, with low testosterone; and KS-2, with normal testosterone levels. Serum samples for melatonin concentrations were obtained every 15 min from 7 PM to 7 AM in a controlled light-dark environment with simultaneous sleep recordings. All KS patients had elevated gonadotropin levels and decreased melatonin levels. Mean (+/- SD) dark-time nocturnal melatonin levels in KS-1 were 92 +/- 21 pmol/L and were 146 +/- 46 pmol/L in KS-2 compared with 178 +/- 64 pmol/L in controls. Integrated nocturnal melatonin secretion values (AUC) were 64 +/- 14 pmol/min x L x 10(3) in KS-1 and 96 +/- 29 pmol/min x L x 10(3) in KS-2 compared with 116 +/- 42 pmol/min x L x 10(3) in controls. All IGD patients had low gonadotropin and testosterone levels. Their dark-time melatonin levels (286 +/- 26 pmol/L) and the AUC values (184 +/- 15 pmol/min/L x 10(3)) were increased. These data indicate that melatonin secretion is increased in male patients with GnRH deficiency and decreased in low testosterone hypergonadotropic hypogonadal patients. Taken together, our results suggest that both gonadotropins and gonadal steroids modulate melatonin secretion in humans.
J Mol Neurosci 1996
PMID:Abnormal melatonin secretion in male patients with hypogonadism. 887 93

In order to investigate the role of protein synthesis in the testosterone regulation of androgen receptor (AR) levels, in vivo studies were undertaken using the ventral prostate gland from adult male rats castrated 24 h previously. Our results showed that testosterone (400 microg/100 g body weight) increased nuclear AR binding 1 h after administration, whereas the protein synthesis inhibitor cycloheximide (400 microg/100 g body weight) by itself did not alter AR binding. However, concomitant administration of testosterone and cycloheximide blocked the testosterone-induced nuclear AR accumulation after 1 h. To determine if changes in AR binding reflected changes in AR protein levels, immunocytochemical studies were conducted on individually dissected ventral prostatic ducts. Castration 24 h previously induced a decrease in nuclear AR immunostaining when compared to intact animals. Testosterone treatment restored the nuclear staining, particularly at the distal tips of the prostatic ducts. Cycloheximide alone did not change AR immunostaining when compared to castrated vehicle-treated rats, yet it significantly decreased the nuclear AR staining induced by testosterone. Our results suggest that AR is being newly synthesized during testosterone treatment. To determine if the effect of testosterone in the regulation of the AR protein was ultimately due to changes at the messenger RNA (mRNA) levels, steady-state AR mRNA levels were measured. Northern blot analysis of poly A+ mRNA preparations revealed that androgen withdrawal for 24 h increased AR mRNA and that testosterone treatment for 1 h did not alter these increased AR mRNA levels. The inhibition of protein synthesis by cycloheximide did not change AR mRNA, but, when cycloheximide was administered in conjunction with testosterone, AR mRNA levels were significantly decreased. In an attempt to relate these responses to changes in transcriptional activity, the transcription inhibitor actinomycin D was administered in vivo. Whereas simultaneous administration of testosterone and cycloheximide modified AR mRNA and AR protein levels, concomitant administration of testosterone with actinomycin D did not alter these levels. It is therefore unlikely that testosterone modifies the transcription of AR mRNA within 1 h after its administration. Collectively, these results suggest that protein synthesis is involved in the mechanism of testosterone-promoted AR regulation. This protein synthesis-dependent mechanism may be involved in the regulation of the stability and/or the translation of AR mRNA in the prostate.
J Steroid Biochem Mol Biol 1996 Aug
PMID:Autoregulation of androgen receptor protein and messenger RNA in rat ventral prostate is protein synthesis dependent. 891 80

The regulation of the FHG22 gene by sex steroids has been studied in Syrian hamster Harderian gland, an organ with sexual dimorphism in which the FHG22 mRNA is female-specific. Testosterone treatment of females caused irregular inhibitory effects on the FHG22 mRNA levels, whereas male castration originated transitory increases during less than 2 weeks. Treatment of 15 day-castrated males for 1 or 2 days with beta-estradiol-3-benzoate caused a marked stimulation in the FHG22 mRNA levels. The results found in vivo may be explained considering those found in female Harderian gland serum-free primary cell cultures. In the absence of hormones, the FHG22 mRNA levels decreased along the time and neither progesterone, testosterone, or 5 alpha-dihydrotestosterone affected the expression. However, estradiol stimulated the FHG22 mRNA expression in a time and dose-dependent manner: increasing effects were detected between 8-96 h of treatment and the EC50 was about 10(-9) M. The estradiol effect was reverted by the antiestrogen ICI 164,384 or by cycloheximide. We conclude that estradiol stimulates FHG22 mRNA expression in Harderian gland, although other agents may also control the expression in vivo.
Mol Cell Endocrinol 1996 Nov 29
PMID:Hormonal regulation of FHG22 mRNA in Syrian hamster harderian glands: role of estradiol. 902 28

Testosterone exerts important feedback actions on the hypothalamus and pituitary of the male rat to control reproductive hormone secretion. Marked fluctuations occur in plasma-luteinizing hormone (LH) concentrations, hypothalamic gonadotrophin-releasing hormone (GnRH) content and GnRH mRNA expression following castration and it appears as though a stable post-castration equilibrium is not attained until 3-4 weeks after gonadectomy. In the present study, we have investigated the effects of long-term (7 week) gonadectomy on GnRH mRNA expression in the male rat and determined whether estrogen or androgen receptor-mediated mechanisms are involved in regulating its expression. Accordingly, in situ hybridization was undertaken using a 35S-labelled antisense oligonucleotide probe complementary to bases 102-149 of the rat GnRH cDNA to quantify cellular GnRH mRNA expression in the medial septum (MS), diagonal band of Broca (DBB) and rostral preoptic area (rPOA) of intact males, rats gonadectomized for 7 weeks and gonadectomized animals implanted with silastic capsules containing testosterone (T), estrogen (E) or dihydrotestosterone (DHT). We found no difference between any of the treatment groups in the number of cells expressing GnRH mRNA in the MS/DBB or rPOA. Similarly, the GnRH mRNA content of cells in the MS/DBB was not different between the treatment groups. In contrast, cellular GnRH mRNA expression in the rPOA was elevated 7 weeks following castration (intact: 0.95 +/- 0.07 silver grains/microm2/cell; gonadectomized: 1.26 +/- 0.03; mean +/- S.E.M., P < 0.05) and this was restored to intact levels by either T (1.02 +/- 0.07) or E (1.02 +/- 0.08) treatment. DHT replacement had no effect on cellular levels of GnRH mRNA in gonadectomized rats (1.26 +/- 0.03). Frequency analysis of relative GnRH mRNA expression/cell showed that the rostral preoptic GnRH population responded to the steroid treatment in an homogeneous manner. These results show that GnRH mRNA expression is elevated specifically within the rPOA of the long-term gonadectomized male rat when LH secretion has stabilized at a constant high level. Further, we show that the gonadal steroid regulation of cellular GnRH mRNA content at such time occurs only through an estrogen receptor-mediated pathway.
Brain Res Mol Brain Res 1997 Jul
PMID:Regulation of preoptic area gonadotrophin-releasing hormone (GnRH) mRNA expression by gonadal steroids in the long-term gonadectomized male rat. 922 9

We have shown previously that chronic treatment with glucocorticoids enhances both ACTH-induced cAMP production and ACTH- or 8Br-cAMP-induced steroidogenesis of cultured ovine adrenocortical cells. This treatment has been shown to involve an increase in the number of ACTH receptors. The present study aimed to explore the mechanism of this effect of glucocorticoids on ACTH receptors. Ovine adrenocortical cells expressed one major ACTH receptor transcript of 3.6 kb and three minor ones of 4.2, 1.8 and 1.3 kb. Dexamethasone treatment of cultured cells increased the levels of all these transcripts in a time- and dose-dependent manner, with an EC50 of (1.5 +/- 0.6) x 10(-8) M. The mean increase over control with 10(-6) M dexamethasone was 144 +/- 11% (n = 14). This enhancing effect was specific for glucocorticosteroids. The antiglucocorticoid Ru38486 blocked the effect of dexamethasone. Testosterone did not modify, while high concentrations of 17 beta-estradiol decreased, ACTH receptor mRNA levels. Treatment of cells with aminoglutethimide (an inhibitor of steroidogenesis) resulted in a dose-dependent decrease in ACTH receptor mRNA levels, which was prevented by concomitant treatment with dexamethasone. Treatment with ACTH also increased ACTH receptor mRNA levels more than twofold. Addition of aminoglutethimide together with ACTH resulted in a smaller increase than that achieved with ACTH alone. Neither dexamethasone nor ACTH modified ACTH receptor mRNA half-lives. However, these two hormones enhanced the levels of both newly synthesized and total ACTH receptor mRNAs. These results indicate that the positive trophic effect of glucocorticoids on ovine adrenocortical cells involves an enhancement of the transcription rate of the ACTH receptor gene. In addition, they suggest that part of the trophic action of ACTH on ACTH receptors may be mediated by ACTH-induced steroidogenesis.
J Mol Endocrinol 1997 Aug
PMID:Glucocorticoids enhance corticotropin receptor mRNA levels in ovine adrenocortical cells. 927 58

Primary cultures of juvenile eel (Anguilla anguilla) pituitary cells were used to study the direct effects of sex steroids on gonadotropin (GtH-II) cell content and release (radioimmunoassay) as well as on mRNAs levels for alpha and GtH-II beta-subunits (dot-blot). Testosterone stimulated GtH-II production in a dose- and time-dependent manner by selectively increasing mRNAs for GtH-II beta-subunit but not alpha-subunit. This positive effect was also induced by non-aromatizable androgens (androstanediol and dihydrotestosterone) but not by estradiol, indicating an androgen-specific effect in the eel. The androgen-specific stimulation of eel GtH-II beta appears closer to the regulation of mammalian follicle stimulating hormone-beta (FSHbeta) than that of salmonid GtH-II beta or mammalian luteinizing hormone-beta (LHbeta)-subunits. Comparison with previous in vivo experiments suggests multiple sites of action of sex steroids on the brain-pituitary gonadotropic axis for the positive feedback on GtH-II synthesis in this juvenile fish.
Mol Cell Endocrinol 1997 Aug 08
PMID:Androgens stimulate gonadotropin-II beta-subunit in eel pituitary cells in vitro. 929 74


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