scispace - formally typeset
Search or ask a question
Topic

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.


Papers
More filters
01 May 2012
TL;DR: In this paper, the authors used a previously described animal model of MetS, obtained by feeding male rabbits a high-fat diet (HFD) for 12 weeks, and found that the ratio between testosterone and estradiol plasma level retains a significant, negative, association with all the fibrosis and most of inflammatory markers analyzed.
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.

148 citations

Journal ArticleDOI
TL;DR: This work investigated androgen generation in human adipose tissue, including expression of 17-hydroxysteroid dehydrogenase (17-HSD) isozymes, important regulators of sex steroid metabolism.
Abstract: Women with polycystic ovary syndrome (PCOS) have high circulating androgens, thought to originate from ovaries and adrenals, and frequently suffer from the metabolic syndrome including obesity. However, serum androgens are positively associated with body mass index (BMI) not only in PCOS, but also in simple obesity, suggesting androgen synthesis within adipose tissue. Thus we investigated androgen generation in human adipose tissue, including expression of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes, important regulators of sex steroid metabolism. Paired omental and subcutaneous fat biopsies were obtained from 27 healthy women undergoing elective abdominal surgery (age range 30-50 years; BMI 19.7-39.2 kg/m(2)). Enzymatic activity assays in preadipocyte proliferation cultures revealed effcient conversion of androstenedione to testosterone in both subcutaneous and omental fat. RT-PCR of whole fat and preadipocytes of subcutaneous and omental origin showed expression of 17beta-HSD types 4 and 5, but no relevant expression of 17beta-HSD types 1, 2, or 3. Microarray analysis confirmed this expression pattern (17beta-HSD5>17beta-HSD4) and suggested a higher expression of 17beta-HSD5 in subcutaneous fat. Accordingly, quantitative real-time RT-PCR showed significantly higher expression of 17beta-HSD5 in subcutaneous compared with omental fat (P<0.05). 17beta-HSD5 expression in subcutaneous, but not omental, whole fat correlated significantly with BMI (r=0.51, P<0.05). In keeping with these findings, 17beta-HSD5 expression in subcutaneous fat biopsies from six women taking part in a weight loss study decreased significantly with weight loss (P<0.05). A role for 17beta-HSD5 in adipocyte differentiation was further supported by the observed increase in 17beta-HSD5 expression upon differentiation of stromal preadipocytes to mature adipocytes (n=5; P<0.005), which again was higher in cells of subcutaneous origin. Functional activity of 17beta-HSD5 also significantly increased with differentiation, revealing a net gain in androgen activation (androstenedione to testosterone) in subcutaneous cultures, contrasting with a net gain in androgen inactivation (testosterone to androstenedione) in omental cultures. Thus, human adipose tissue is capable of active androgen synthesis catalysed by 17beta-HSD5, and increased expression in obesity may contribute to circulating androgen excess.

148 citations

Journal ArticleDOI
TL;DR: It is concluded that through reduction of the levels of inhibitory glucocorticoids, 11HSD has a novel role among Leydig cell steroid-metabolizing enzymes in the regulation of T production.
Abstract: Leydig cells from mature rat testes contain high levels of 11 beta-hydroxysteroid dehydrogenase (11HSD), an enzyme that oxidatively inactivates glucocorticoids. We have proposed that the 11HSD of Leydig cells protects the testis from the effects of high levels of glucocorticoids, as may occur in stress and Cushing's disease. In this paper we investigate whether testicular 11HSD by inactivating glucocorticoids diminishes their ability to inhibit testosterone (T) production. Corticosterone (B) and dexamethasone (DEX) inhibited T production by purified Leydig cells in a dose-dependent manner. Activity was diminished by 50% with 1.5 nM DEX vs. 0.4 microM B. The shapes of the inhibition curves were consistent with a saturable process; inhibition by both steroids was overcome with the glucocorticoid receptor antagonist RU486. We concluded that the effect was mediated by glucocorticoid receptors. Aldosterone, 11 beta-hydroxyprogesterone, and 11-deoxycorticosterone did not decrease T production. The greater poten...

148 citations

Journal ArticleDOI
TL;DR: The fetal testis has highest Leydig cell and endogenous steroid concentrations and the new Leydigs cell generation after 15 days has a persistently low steroid concentration through puberty.
Abstract: Endogenous androgens (androstenedione, testosterone, 5a-dihydrotestosterone and 5a-androstane-3a,1713-diol), and some of their C21 precursors (pregnenolone, progesterone and 17-hydroxyprogesterone) were measured in rat testes between Day 18.5 of pregnancy and Day 64 postpartum, and correlated with numerical densities of Leydig cells. The latter parameter showed an early maximum on Day 19.5 of the fetal period, a nadir on Day 15 postpartum, and a gradual increase thereafter. The two dominating androgens, testosterone and 5a-androstane-3a,17(3-diol, had similar levels until 15 days of age, but the 5a-diol predominated thereafter. The total steroid content per Leydig cell was highest on Day 18.5 of gestation (77 ng/10’ cells). A decline started already in utero, and reached a nadir of 5 ng/10’ cells on Day 29. Thereafter, a slight increase occurred with advancing age. It is concluded that: 1) The fetal testis has highest Leydig cell and endogenous steroid concentrations. A nadir in these parameters is seen 2-4 wk postpartum. The Leydig cell concentration increases around puberty on Days 40-60, but only a slight concomitant increase occurs in steroids. 2) A sharp decline in steroid content per Leydig cell occurs during the last fetal days, but the postnatal decline of testicular steroids is due to Leydig cell loss. 3) The new Leydig cell generation after 15 days has a persistently low steroid concentration through puberty. 4) The relative proportions of endogenous steroids are similar in the fetal and immature testes, but the pubertal increase in steroidogenesis is characterized by increased ratios of C19/C21 steroids, 5a-reduced/3-keto-4-ene androgens, and 1 7�3-hydroxy/1 7-keto androgens.

148 citations

Journal ArticleDOI
TL;DR: Abdominal obesity appears to be associated with slight hypocortisolemia and increased sensitivity to exogenous adrenocorticotropin stimulation, which may contribute to the hyperinsulinemia and related metabolic changes including decreased SHBG levels in males.
Abstract: Sex hormone-binding globulin (SHBG) is a plasma glycoprotein with high binding affinity for testosterone and dihydrotestosterone and lower affinity for estradiol. SHBG is synthesized in the liver, and its plasma level is important in the regulation of plasma free and albumin-bound androgens and estrogens. Obesity and particularly excess visceral fat, known risk factors for cardiovascular and metabolic diseases, are associated with decreased testosterone levels in males and SHBG levels in both sexes. SHBG is usually positively correlated with high-density lipoprotein cholesterol and negatively correlated with triglyceride and insulin concentrations. A positive association between SHBG and various measures of insulin sensitivity has been demonstrated in both sexes, suggesting that decreased SHBG levels may be one of the components of the metabolic syndrome. We have examined pituitary-adrenocortical function, glucose tolerance, and lipoprotein and hormone levels in a large cohort of Finnish males. Abdominal obesity appears to be associated with slight hypocortisolemia and increased sensitivity to exogenous adrenocorticotropin stimulation, which may contribute to the hyperinsulinemia and related metabolic changes including decreased SHBG levels in males.

148 citations


Network Information
Related Topics (5)
Estrogen
40.7K papers, 1.7M citations
92% related
Adipose tissue
54.6K papers, 2.5M citations
83% related
Estrogen receptor
34.2K papers, 1.4M citations
82% related
Insulin
124.2K papers, 5.1M citations
82% related
Thyroid
68.8K papers, 1.5M citations
82% related
Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20224
2021509
2020435
2019438
2018456
2017505