Testosterone

About: Testosterone is a research topic. Over the lifetime, 23258 publications have been published within this topic receiving 808079 citations. The topic is also known as: 4-androsten-17beta-ol-3-one & 4-Androsten-3-one-17b-ol.

Di(n-butyl) phthalate impairs cholesterol transport and steroidogenesis in the fetal rat testis through a rapid and reversible mechanism.

Abstract: In utero exposure to di(n-butyl) phthalate (DBP) leads to a variety of male reproductive abnormalities similar to those caused by androgen receptor antagonists. DBP demonstrates no affinity for the androgen receptor, but rather leads to diminished testosterone production by the fetal testis. The purpose of this study was to determine the onset and reversibility of DBP effects on the fetal testis and to determine at a functional level the points in the cholesterol transport and steroidogenesis pathways affected by DBP. Starting at gestational day (gd) 12, pregnant rats were gavaged daily with 500 mg/kg DBP or corn oil control. Significant decreases in testosterone production and mRNA expression of scavenger receptor B1, P450(SCC), steroidogenic acute regulatory protein, and cytochrome p450c17 were observed as early as gd 17. Testosterone, mRNA, and protein levels remained low 24 h after withdrawal of DBP treatment but increased 48 h after cessation of DBP exposure. In another experiment, pregnant dams were treated with DBP until gd 19, with the start of DBP treatment moved 1 d later into gestation for each treatment group, with the final group dosed only on gd 19. Significant decreases in testosterone, mRNA expression, and protein expression were evident as early as 3 h after treatment with DBP, with full repression apparent 24 h after treatment. Using a testis explant system, we determined that DBP treatment led to diminished transport of cholesterol across the mitochondrial membrane as well as diminished function at each point in the testosterone biosynthesis pathway except 17 beta-hydroxysteroid dehydrogenase. The transcriptional repression caused by DBP does not appear to be mediated via interference with steroidogenic factor-1 as determined by reporter assays. We conclude that high-dose DBP exposure leads to rapid and reversible diminution of the expression of several proteins required for cholesterol transport and steroidogenesis in the fetal testis, resulting in decreased testosterone synthesis and consequent male reproductive maldevelopment.

In Utero Exposure to Di-(2-ethylhexyl) Phthalate Exerts Both Short-Term and Long-Lasting Suppressive Effects on Testosterone Production in the Rat

Abstract: We examined the effects of fetal exposure to a wide range of di-(2-ethylhexyl) phthalate (DEHP) doses on fetal, neonatal, and adult testosterone production. Pregnant rats were administered DEHP from Gestational Day (GD) 14 to the day of parturition (Postnatal Day 0). Exposure to between 234 and 1250 mg/kg/day of DEHP resulted in increases in the absolute volumes of Leydig cells per adult testis. Despite this, adult serum testosterone levels were reduced significantly compared to those of controls at all DEHP doses. Organ cultures of testes from GD20 rats exposed in utero to DEHP showed dose-dependent reductions in basal testosterone production. Surprisingly, however, no significant effect of DEHP was found on hCG-induced testosterone production by GD20 testes, suggesting that the inhibition of basal steroidogenesis resulted from the alteration of molecular events upstream of the steroidogenic enzymes. Reduced fetal and adult testosterone production in response to in utero DEHP exposure appeared to be unrelated to changes in testosterone metabolism. In view of the DEHP-induced reductions in adult testosterone levels, a decrease in the expression of steroidogenesis-related genes was anticipated. Surprisingly, however, significant increases were seen in the expression of Cyp11a1, Cy17a1, Star, and Tspo transcripts, suggesting that decreased testosterone production after birth could not be explained by decreases in steroidogenic enzymes as seen at GD20. These changes may reflect an increased number of Leydig cells in adult testes exposed in utero to DEHP rather than increased gene expression in individual Leydig cells, but this remains uncertain. Taken together, these results demonstrate that in utero DEHP exposure exerts both short-term and long-lasting effects on testicular steroidogenesis that might involve distinct molecular targets in fetal and adult Leydig cells.

Regulation by steroid hormones of phosphorylation of specific protein common to several target organs

Abstract: The effect of in vivo administration of steroid hormones on the endogenous phosphorylation of individual proteins in cell sap from several target tissues has been studied using the technique of discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The hormones studied (and their respective target organs) were: 17 beta-estradiol [1,3,5(10)-estratriene-3, 17beta-diol] (uterus); testosterone (17 beta-hydroxy-4-androsten-3-one) (ventral prostate and seminal vesicle)' cortisol (11beta, 17alpha, 21-trihydroxy-4-pregnene-3,20-dione) (liver); aldosterone (the 18.11-hemiacetal of 11beta,21-dihydroxy-3,20-dioxo-4-pregnen-18-al) (toad bladder). In each of the five target organs studied, pretreatment with the appropriate hormone reduced the amount of 32P incorporated from [gamma-32P]ATP into an apparently common protein band present in the cytosol fraction. The endogenous phosphorylation and dephosphorylation of this protein was also regulated by cAMP. This protein, designated SCARP (steroid and cyclic adenosine 3':5' monophosphate regulated phosphoprotein), was estimated to have an apparent molecular phoprotein), was estimated to have an apparent molecular weight of 54,000 in the gel electrophoresis system used. The effect of the steroid hormones in decreasing the phosphorylation of SCARP was specific for their respective target tissues. The effect of 17beta-estradiol and of testosterone on SCARP could be observed as early as two hours after a single dose of the steroid. A protein synthesis inhibitor, cycloheximide, abolished the effect of the steroid hormones, but not that of cAMP, on the endogenous phosphorylation of SCARP. The results suggest that steroid hormones regulate either the amount of SCARP or its ability to become phosphorylated. This regulation of a single species of protein by several types of steroid hormones in different target organs raises the possibility that this common biochemical action may be a component of the mechanism by which these steroids achieve some of their biological effects.

Identification of virilizing adrenal tumors in hirsute women.

Abstract: Background Hirsutism in women is usually caused by benign adrenal or ovarian disorders, but it can also be caused by adrenal carcinoma. The most effective way to identify such carcinomas is not known. Methods We measured serum and urinary steroids before and after the administration of 3 mg of dexamethasone per day for five days in 14 hirsute women with histologically proved adrenal tumors (12 adrenal carcinomas and 2 adrenal adenomas) and in 73 women with hirsutism of non-neoplastic origin. Results All the women with adrenal tumors had elevated basal serum concentrations of testosterone or dehydroepiandrosterone sulfate, as compared with 36 of the 73 women with non-neoplastic hirsutism (sensitivity, 100 percent; 95 percent confidence interval, 77 to 100; specificity, 50 percent; 95 percent confidence interval, 38 to 62). After the administration of dexamethasone, serum dehydroepiandrosterone sulfate concentrations and urinary 17-ketosteroid excretion decreased to values similar to those in normal women i...

Mechanisms Behind Insulin Resistance in Rat Skeletal Muscle After Oophorectomy and Additional Testosterone Treatment

Abstract: The absence of female sex hormones, as well as testosterone treatment of oophorectomized (OVX) female rats has been demonstrated to result in decreased whole-body insulin-mediated glucose uptake. The cellular mechanism behind this insulin resistance and the role of low levels of female sex hormones as a risk factor for development of peripheral insulin resistance are not yet fully clarified. We assessed the protein expression of GLUT4 and glycogen synthase, as well as insulin-induced translocation of GLUT4 to the plasma membrane, in soleus skeletal muscle from control rats, OVX rats, and OVX rats treated for 8 weeks with testosterone (OVX + T). Whole-body insulin-mediated glucose uptake assessed by the hyperinsulinemic-euglycemic clamp procedure was 25% lower in OVX rats ( P P P P P