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.

Fetal death in mice lacking 5α-reductase type 1 caused by estrogen excess

Abstract: Female mice deficient in steroid 5α-reductase type 1 have a decreased litter size. The average litter in homozygous deficient females is 2.7 pups vs. 8.0 pups in wild type controls. Oogenesis, fertilization, implantation, and placental morphology appear normal in the mutant animals. Fetal loss occurs between gestation days 10.75 and 11.0 commensurate with a midpregnancy surge in placental androgen production and an induction of 5α-reductase type 1 expression in the decidua of wild type mice. Plasma levels of androstenedione and testosterone are 2- to 3-fold higher on gestation day 9, and estradiol levels are chronically elevated by 2- to 3-fold throughout early and midgestation in the knockout mice. Administration of an estrogen receptor antagonist or inhibitors of aromatase reverse the high rate of fetal death in the mutant mice, and estradiol treatment of wild type pregnant mice causes fetal wastage. The results suggest that in the deficient mice, a failure to 5α-reduce androgens leads to their conversi...

Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial

Abstract: Context: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are the major circulating adrenal steroids and substrates for peripheral sex hormone biosynthesis. In Addison’s disease, glucocorticoid and mineralocorticoid deficiencies require lifelong replacement, but the associated near-total failure of DHEA synthesis is not typically corrected. Objective and Design: In a double-blind trial, we randomized 106 subjects (44 males, 62 females) with Addison’s disease to receive either 50 mg daily of micronized DHEA or placebo orally for 12 months to evaluate its longer-term effects on bone mineral density, body composition, and cognitive function together with well-being and fatigue. Results: Circulating DHEAS and androstenedione rose significantly in both sexes, with testosterone increasing to low normal levels only in females. DHEA reversed ongoing loss of bone mineral density at the femoral neck (P < 0.05) but not at other sites; DHEA enhanced total body (P = 0.02) and truncal (P = 0.017) lean mass signif...

Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit.

Abstract: Metabolic syndrome (MetS) and benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) are often associated. One of their common denominators is hypogonadism. However, testosterone supplementation is limited by concerns for potential prostatic side effects. The objective was to determine whether MetS-associated prostate alterations are prevented by testosterone supplementation. We used a previously described animal model of MetS, obtained by feeding male rabbits a high-fat diet (HFD) for 12 weeks. Subsets of HFD rabbits were treated with testosterone or with the farnesoid X receptor agonist INT-747. Rabbits fed a standard diet were used as controls. HFD-animals develop hypogonadism and all the MetS features: hyperglycemia, glucose intolerance, dyslipidemia, hypertension, and visceral obesity. In addition, HFD-animals show a prostate inflammation. Immunohistochemical analysis demonstrated that HFD-induced prostate fibrosis, hypoxia, and inflammation. The mRNA expression of several proinflammatory (IL8, IL6, IL1b, and TNFa), T lymphocyte (CD4, CD8, Tbet, Gata3, and ROR gt), macrophage (TLR2, TLR4, and STAMP2), neutrophil (lactoferrin), inflammation (COX2 and RAGE), and fibrosis/myofibroblast activation (TGFb, SM22a, aSMA, RhoA, and ROCK1/ROCK2) markers was significantly increased in HFD prostate. Testosterone, as well as INT-747, treatment prevented some MetS features, although only testosterone normalized all the HFD-induced prostate alterations. Interestingly, the ratio between testosterone and estradiol plasma level retains a significant, negative, association with all the fibrosis and the majority of inflammatory markers analyzed. These data highlight that testosterone protects rabbit prostate from MetS-induced prostatic hypoxia, fibrosis, and inflammation, which can play a role toward the development/progression of BPH/LUTS.

Blockade of Testosterone-Induced Mounting Behavior in the Male Rat with Intracranial Application of the Aromatization Inhibitor, Androst-l,4,6-triene-3,17-dione

Abstract: Propylene glycol (glycol) solutions containing either testosterone (T) or estradiol (E2) were infused directly into the preoptic area (POA) of longterm castrated rats in order to reinstate male copulatory behavior. In addition, castrated males were administered T or E2 in the POA in combination with a steroid that has been shown to block the aromatization of testosterone to estradiol, androstl, 4,6-triene-3,17-dione (ATD). The facilitatory action of testosterone on mounting behavior was blocked when it was given in combination with ATD. Animals treated in the POA with glycol † T, glycol † E2, or ATD 4- E2 all showed significant increases in mounting behavior over preimplant levels. There was no significant rise in the number of intromissions or ejaculations in any of the treatment groups. These results support the hypothesis that, at least for mounting behavior, aromatization is necessary for the stimulation of male sexual behavior by testosterone. (Endocrinology 97: 1545, 1975)

Significance of mutations in the androgen receptor gene in males with idiopathic infertility.

Abstract: Abnormal human spermatogenesis is caused by a variety of genetic and acquired conditions. Because spermatogenesis is dependent on androgens, some males may have a minimal form of androgen insensitivity that does not inhibit virilization but impairs fertility. This has lead us to investigate the possibility of abnormalities in the androgen receptor (AR) gene in a large cohort of males suffering from infertility of unknown cause. We studied 180 males with variable impairment of spermatogenesis. In all patients, serum levels of testosterone and gonadotropins were analyzed to define an androgen sensitivity index (ASI). Single-strand conformation analysis and direct DNA sequencing of PCR-amplified blood leukocyte DNA were used to identify mutations within the whole coding region of the AR-gene. Endocrine and molecular investigations were compared with 53 normal males with proven fertility. In three infertile males, mutations in the AR were identified. Two unrelated males had the same variation within the first exon encoding for the transactivation domain of the receptor (Pro390Ser), whereas, in the third, a mutation in the hormone-binding region was characterized (Gln798Glu). All identified mutation carriers had a significantly elevated ASI. A proportion of males with idiopathic infertility carry relevant variations within the AR-gene. These males may be distinguished on the basis of hormone levels, calculating the ASI, although this index lacks specificity.