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

The potential biosynthetic capacity of testicular hormones was studied in immature, pubertal and aging guinea-pig. In their sexual development towards puberty, changes in the relationship of the steroids involved in the steroidogenic pathways were observed. The testosterone/androstenedione ratio changes markedly, showing an important increase with pubertal proximity. The testosterone in equilibrium androstenedione sequence, reversibly catalyzed by 17 beta-hydroxysteroid oxidoreductase (17 beta-oxido-reductase), clearly shifted towards androstenedione in immature animals irrespective of the precursor utilized. Post-pubertal animals showed a greater enzymatic activity in the 5-ene and 4-ene testicular synthesis pathways, testosterone production being greatest. In the aging animal, hormonal biosynthetic capacity falls. Reversion of the 17 beta-oxido-reductase activity could be one of the mechanisms responsible for the decrease in testosterone, as in immature guinea-pigs. In order to investigate the in vitro steroidogenic capacity of glands at different ages, minces of testicular tissue were incubated with labelled precursors. The studies were conducted in triplicate at 35 degrees C. For equal quantities of incubated tissue the non-metabolized amount of [3H]pregnenolone and [14C]progesterone, utilized as precursors, was different in post-pubertal and senescent animals: 55.7 +/- 3 vs 59.3 +/- 2.3% (P less than 0.01) for pregnenolone, and 50.1 +/- 3.3 vs 56.3 +/- 2.9% (P less than 0.01) for progesterone, respectively. Testosterone production was 12 +/- 2% in adult and 6.7 +/- 2.7% in senescent animals (P less than 0.01). The testosterone/androstenedione ratio was not significantly different in post-pubertal and senescent animals: 2.8 +/- 0.5 vs 2.4 +/- 0.4, but consistently higher than found in immature animals: 0.3 +/- 0.1. The lesser potential capacity of the aging tissue to synthesize testosterone could be explained by a decline in the glands capacity to metabolize the hormonal precursors.
J Steroid Biochem Mol Biol 1991 Feb
PMID:Biosynthesis of testicular steroids in the immature, adult and senescent guinea-pig. 200 45

To investigate the influence of fetal sex on maternal testosterone levels throughout pregnancy, blood was sampled from 37 healthy pregnant women from week 14 until term and at 6 weeks postpartum. Testosterone concentrations were measured with a highly specific RIA after chromatographic purification. Mean (+/- SD) testosterone at the end of gestation was significantly higher compared to non-pregnant values (3.10 +/- 2.38 mM/l, n = 32 vs 1.14 +/- 1.06 nM/l, n = 35). It appeared that in women carrying a male fetus testosterone levels gradually increased during pregnancy up to 3.99 +/- 2.72 nM/l. In women carrying a female fetus the levels decreased after the first trimester from 2.44 nM/l to 1.80 nM/l. A statistically significant difference (P less than 0.01) existed in maternal testosterone concentrations between both groups during the second half of pregnancy.
J Steroid Biochem Mol Biol 1991 Jul
PMID:Maternal testosterone and fetal sex. 206 66

The profile of hepatic microsomal cytochrome P450 expressed in the male and female rat was dramatically altered by streptozotocin-induced diabetes. In the diabetic male, P450 forms IIC11, IIC13, IIA2, and IIIA2 were suppressed and forms IIA1 and IIC12 were induced to the levels observed in the immature male rat. A 6- to 8-fold induction of P450 IIE1 was detected in both male and female diabetic rats. A member of the P450 IIIA family was also induced in the diabetic female rat. Accompanying the change in P450 profile in the diabetic male rat was reduction in circulating testosterone and tetraiodothyronine concentrations and a sharp diminution of the normally pulsatile pattern of growth hormone secretion. In contrast to the male rat, the growth hormone secretion pattern in the diabetic female rat was unchanged from control. The hormone and P450 profiles detected in the diabetic male rat suggest a reversion to an immature physiological state. Testosterone replacement treatments carried out for 2 weeks slightly but significantly affected the suppression of P450 IIC11 and reversed the changes in P450 IIA2, IIIA2, and IIC12 in the diabetic male, without altering the suppressed state of growth hormone secretion. However, 1 week of human growth hormone, administered intravenously every 4 hr to diabetic male rats, failed to significantly reverse the diabetes-induced changes in hepatic cytochromes P450, in particular forms IIC11 and IIE1, despite the presence of an episodic plasma hGH profile. An induction of P450 IIE1 in diabetic female rats, without a reduction in growth hormone secretion, suggests that its induction in diabetes in both sexes is not related to changes in growth hormone. In addition, the results of testosterone treatment on the expression of IIC12, IIA2, and IIIA2 in the diabetic male rat suggest a regulatory role for this hormone that does not involve the pituitary secretion of growth hormone. However, the lack of effect of human growth hormone treatment in the diabetic male on levels of individual P450 forms indicates that in diabetes there may be a change in the ability of the male rat hepatocyte to respond to a somatic signal, possibly as a result of the changes in other hormone factors.
Mol Pharmacol 1990 Jan
PMID:Effects of testosterone and growth hormone treatment on hepatic microsomal P450 expression in the diabetic rat. 210 52

Benzodiazepines have been shown to competitively inhibit morphine glucuronidation in rat and human hepatic microsomes. Flunitrazepam exerted a potent competitive inhibition of rat hepatic morphine UDP-glucuronosyltransferase (UDPGT) activity (Ki = 130 microM). It has no effect on the activity of p-nitrophenol, 17 beta-hydroxysteroid, 3 alpha-hydroxysteroid, or 4-hydroxybiphenyl UDPGTs. Because flunitrazepam is an effective photoaffinity label for benzodiazepine receptors, studied were performed in solubilized rat hepatic microsomes and with partially purified preparations of morphine UDPGT to determine the enhancement of flunitrazepam inhibition and binding to morphine UDPGT promoted by exposure to UV light. Under UV light, flunitrazepam inhibition was markedly enhanced. UV light exposure also led to a marked increase in binding of [3H]flunitrazepam to microsomal protein, which was protected substantially by preincubation with morphine. Testosterone, androsterone, and UDP-glucuronic acid did not protect against UV-enhanced flunitrazepam binding, and morphine did not reverse flunitrazepam binding once binding had occurred. As morphine UDPGT was purified, a good correlation was found between the increases in specific activity of morphine UDPGT and flunitrazepam binding to protein. Chromatofocusing chromatography showed that flunitrazepam bound only to fractions containing active morphine UDPGT, and no binding to 4-hydroxybiphenyl UDPGT was observed. Fluorography of a sodium dodecyl sulfate-polyacrylamide electrophoresis gel of solubilized hepatic microsomes that had been treated with [3H] flunitrazepam under UV light revealed a band with a monomeric molecular weight between 54,000 and 58,000. This monomeric molecular weight compares favorably with the reported monomeric molecular weight of homogeneous morphine UDPGT (56,000). These studies suggest that flunitrazepam binds rather selectively to the morphine binding site of morphine UDPGT and may prove to be a useful probe for this enzyme.
Mol Pharmacol 1990 Sep
PMID:Photoaffinity labeling of rat liver microsomal morphine UDP-glucuronosyltransferase by [3H]flunitrazepam. 211 76

We have shown previously that androgens negatively regulate LH alpha and beta-subunit mRNA levels, but have little or no effect on FSH beta mRNA levels in rats in vivo. In contrast, estrogen negatively regulates all three gonadotropin subunit mRNA levels in vivo. We have examined the effects of these sex steroids on gonadotropin subunit synthesis directly at the level of the pituitary gland by using cultured rat pituitary cells. Adult female and male rat pituitaries were dissected, dispersed enzymatically, and maintained in culture for 2 days. At that time, cells were treated for varying lengths of time with either medium alone or sex-steroid hormone treatments (estradiol or testosterone). Dose-response and time-course experiments were performed. Cells were then harvested and total RNA was extracted. Gonadotropin subunit mRNA levels were assessed by blot hybridization techniques. Sex-steroid hormones were added to achieve final concentrations ranging from 10(-12) to 10(-6) M for dose response experiments and 10(-8) M for time-course experiments. Testosterone treatment (10(-8) M) increased FSH beta mRNA levels 3-fold in females (P less than 0.01) and males (P less than 0.05), but had no effect on alpha or LH beta mRNA levels in either sex. Dose-related increases in FSH beta mRNA levels with increasing concentrations of testosterone were observed in both female and male pituitary cell cultures. Time-course studies revealed that the testosterone-stimulated increases in FSH beta mRNA levels are statistically significant by 12 h and 6 h after hormone addition in female and male cultures, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 Nov
PMID:Androgens positively regulate follicle-stimulating hormone beta-subunit mRNA levels in rat pituitary cells. 212 39

Motoneurons express calcitonin gene-related peptide (CGRP). Previous studies have shown that CGRP immunoreactivity is regulated by testosterone in the androgen-sensitive motoneurons of the spinal nucleus of the bulbocavernosus (SNB). In this research the effect of plasma levels of testosterone on the expression of alpha CGRP mRNA in the SNB motoneurons of adult male rats was studied with in situ hybridization. The number of motoneurons expressing alpha CGRP mRNA and the level of alpha CGRP mRNA expression was significantly higher in the SNB of castrated male rats than in the SNB of gonadally intact rats. Using a 5x background labeling criterion in castrated rats 88.1 +/- 4.5% while in intact rats 75.3 +/- 6.4% of SNB motoneurons expressed alpha CGRP mRNA. Testosterone replacement at the time of castration prevented the effect of castration on the expression of alpha CGRP mRNA in SNB motoneurons. In castrated rats, the increase in the number of SNB cells expressing CGRP was the result of increased steady state levels of alpha CGRP mRNA in all SNB neurons.
Brain Res Mol Brain Res 1990 Jul
PMID:Steroid regulation of calcitonin gene-related peptide mRNA expression in motoneurons of the spinal nucleus of the bulbocavernosus. 216 68

Expression of the c-myc gene was studied in the livers of male and female Wistar rats. Furthermore, the effects on hepatic c-myc expression of neonatal and adult castration, with or without testosterone supplementation, as well as of continuous administration of GH to intact males, were analysed. Expression of c-myc was low in 6-day-old animals of both sexes, reached a maximum at 35 days of age and declined to the level of adult animals at 70 days. In prepubertal animals, expression was higher in females, but was higher in males after the onset of puberty, the postpubertal female rat liver exhibiting 50-70% of the expression in males. Treatment of adult male rats with bovine GH in osmotic minipumps for 1 week reduced c-myc expression to the level of female rats. Castration, both neonatally and of adults, also feminized hepatic c-myc expression. Testosterone supplementation of the castrated animals increased the expression towards the level in sham-operated controls. These results indicate that the c-myc gene is regulated by the hypothalamo-pituitary-liver axis via the sex-differentiated pattern of GH secretion, in analogy with other sex-differentiated hepatic functions, such as metabolism of steroids and xenobiotics. Neuroendocrine regulation of a gene such as c-myc, which is involved in the control of cell proliferation and differentiation, represents another aspect of the complex influence of GH on various somatic functions.
J Mol Endocrinol 1990 Dec
PMID:Hypothalamo-pituitary regulation of the c-myc gene in rat liver. 228 38

We have previously reported that testosterone decreased ornithine decarboxylase (ODC) activity in primary cultures of rat Sertoli cells. In this report we examined the mechanism of this reduction. In cells pretreated with testosterone (5 x 10(-7) M) for 48 h before the start of the experiment ODC activity was decreased, on the average, 43% at all time points examined. ODC mRNA levels were also decreased an overall 33%. The testosterone-mediated decrease in ODC activity was first seen 8 h after the addition of testosterone to the cells. Testosterone had no significant affect on the levels of actin or transferrin mRNA. The effect of testosterone was androgen specific. Neither ODC activity nor mRNA was affected by the nonandrogenic steroids progesterone or cortisol. These results suggest that testosterone decreases ODC mRNA in Sertoli cells either through an inhibition of transcription or through a decrease in message stability. Testosterone does not appear to affect ODC mRNA translation, since the percent decreases in ODC activity and mRNA in response to testosterone were essentially equivalent. Regulation of Sertoli cell ODC expression by testosterone may reflect one mechanism by which Sertoli cell function is integrated with surrounding cell types. The Sertoli cell, unlike any other cell, secretes putrescine, the product of ODC catalysis of ornithine. We suggest that the modulation of ODC by testosterone and, hence, the amount of putrescine secreted by the Sertoli cell may be significant in the process of spermatogenesis.
Mol Endocrinol 1990 Aug
PMID:Testosterone decreases ornithine decarboxylase messenger RNA levels in primary cultures of rat Sertoli cells. 229 29

The gene encoding the opioid peptide precursor preproenkephalin is expressed at high levels in the initial segment of the adult rat epididymis. Expression is localized to principal cells, the secretory epithelial cells lining the epididymal duct. During development, epididymal proenkephalin mRNA levels show a pronounced increase at about 44 days of age, coincident with the initial entry of spermatozoa into the epididymal lumen. Hypophysectomy leads to a 60-fold decrease in epididymal proenkephalin mRNA levels. Testosterone replacement can prevent this decline in a manner consistent with an effect upon spermatogenesis. Castration studies demonstrate that a gonadal factor other than testosterone directly regulates epididymal proenkephalin expression, and the results of efferent duct ligation suggest that this factor must be supplied through an intact connection of the testis and epididymis. Proenkephalin mRNA levels in the epididymis correlate with the decline and reappearance of spermatozoa induced by the alkylating agent busulphan. Thus, the developmental profile of proenkephalin expression, coupled with the results of both surgical and pharmacological manipulations of the reproductive tract, indicate that spermatozoa, or a spermatozoa-associated factor, regulate proenkephalin gene expression in the epididymis.
Mol Endocrinol 1990 Jan
PMID:A spermatozoa-associated factor regulates proenkephalin gene expression in the rat epididymis. 232 61

The cytochrome P-450-dependent aromatase pathway utilizes the androgens testosterone (T) and androstenedione, as substrates for estrogen formation. In addition, androgens have been shown to influence the level of aromatase activity in various tissues. In cultured human skin fibroblasts, incubation with T for 14 h resulted in a dose-dependent decline in aromatase activity, the concentration of T producing a half-maximal decline being 6 nM. In the presence of T (50 nM), aromatase activity declined in a time-dependent fashion with maximal reduction occurring by 9 h. When aromatase kinetics were determined after preincubation of cells with T, there was a significant decline in the calculated Vmax with no significant change in the apparent Km, suggesting that incubation of cells with T reduced the number of active enzyme sites. Aromatase activity was unaffected by preincubation of cells with the synthetic androgen methyltrienolone. In addition, the decline in aromatase activity following preincubation with T was observed in cells derived from patients with complete androgen insensitivity demonstrating that the effect of T was not mediated by androgen receptors. Furthermore, new protein synthesis was not necessary for the T-mediated effect as the presence of cycloheximide (50 micrograms/ml) did not prevent it. When cells were incubated at low oxygen tension, the inhibition of aromatase activity by T was diminished. Testosterone is rapidly metabolized in genital skin fibroblasts to dihydrotestosterone, androstanedione, androsterone, 3 alpha-androstanediol, 3 beta-androstanediol and estradiol. To determine if a metabolite of T might be responsible for the repression of aromatase activity, aromatase activity was determined in cells following preincubation with various metabolites of T. Preincubation of cells with androstenedione, androstanedione or 3 alpha-androstanediol produced a small but significant decline in aromatase activity, whereas preincubation of cells with dihydrotestosterone, androsterone, or 3 beta-androstanediol did not have a significant effect. Aromatase activity was also unaffected by preincubation of cells with estradiol or diethylstilbestrol. When aromatase activity was assayed in microsomal preparations from cells preincubated with T, activity was reduced. Although cells preincubated with 50 nM [3H]T contained between 0.25 and 0.51 pmol of residual steroid/mg microsomal protein, the amount of [1-3H]androstenedione and T was insufficient to account for the observed decline in aromatase activity on the basis of competitive inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Cell Endocrinol 1990 Mar 05
PMID:Testosterone lowers aromatase activity in cultured human genital skin fibroblasts. 232 27


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