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.

Prevalence of Symptomatic Androgen Deficiency in Men

Abstract: Context: Despite recognition that androgen deficiency in men should be defined according to biochemical and clinical criteria, most prevalence estimates are based on low testosterone levels alone Objective: The objective of this study was to examine the association between symptoms of androgen deficiency and low total and calculated free testosterone levels and estimate the prevalence of symptomatic androgen deficiency in men Design: This study was a population-based, observational survey Participants: A total of 1475 Black, Hispanic, and white men, between the ages of 30–79 yr, with complete data on testosterone, SHBG, and symptoms of androgen deficiency, and who are not taking medications that impact sex steroid levels were randomly selected from the Boston Area Community Health Survey Outcome: Outcomes were measured as symptomatic androgen deficiency, defined as low total (<300 ng/dl) and free (<5 ng/dl) testosterone plus presence of low libido, erectile dysfunction, osteoporosis or fracture, or tw

The androgen receptor in prostate cancer.

Abstract: The androgen receptor is a member of the family of nuclear receptors. In its activated form as an androgen receptor ligand complex (the ligand can either be testosterone or 5a-dihydrotestosterone), the androgen receptor is able to regulate a specific expression of target genes. The androgen receptor is expressed at high levels in male reproductive tissues. Mutations in the androgen receptor gene are the molecular cause of the androgen insensitivity syndrome, which is characterized by an aberrant male or an apparently female phenotype. Expansion of a CAG-repeat, encoding a polymorphic glutamine stretch is the cause of a rare motor neuron disease (Kennedy's disease). Hormonal therapy is the treatment of choice for metastatic prostate cancer. Hormone refractory prostate tumors in general still express androgen receptor. In a proportion of the late stage prostate tumors, somatic mutations in the androgen receptor gene have been described. Mutations can result in diminished ligand specificity of the androgen receptor. Furthermore, it has been hypothesized that ligand independent mechanisms can also be involved in androgen receptor activation.

Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene

Abstract: It is well established that spermatogenesis is controlled by gonadotrophins and testosterone. However, a role for estrogens in male reproduction recently was suggested in adult mice deficient in estrogen receptor α. These mice became infertile primarily because of an interruption of fluid reabsorption by the efferent ductules of the epididymis, thus leading to a disruption of the seminiferous epithelium [Hess, R. A., Bunick, D., Lee, K. H., Bahr, J., Taylor, J. A., Korach, K. S., and Lubahn, D. B. (1997) Nature (London) 390, 509–512]. Despite the demonstration of the aromatase enzyme, which converts androgens to estrogens, and estrogen receptors within the rodent seminiferous epithelium, the role of aromatase and estrogen in germ cell development is unknown. We have investigated spermatogenesis in mice that lack aromatase because of the targeted disruption of the cyp19 gene (ArKO). Male mice deficient in aromatase were initially fertile but developed progressive infertility, until their ability to sire pups was severely impaired. The mice deficient in aromatase developed disruptions to spermatogenesis between 4.5 months and 1 year, despite no decreases in gonadotrophins or androgens. Spermatogenesis primarily was arrested at early spermiogenic stages, as characterized by an increase in apoptosis and the appearance of multinucleated cells, and there was a significant reduction in round and elongated spermatids, but no changes in Sertoli cells and earlier germ cells. In addition, Leydig cell hyperplasia/hypertrophy was evident, presumably as a consequence of increased circulating luteinizing hormone. Our findings indicate that local expression of aromatase is essential for spermatogenesis and provide evidence for a direct action of estrogen on male germ cell development and thus fertility.

Sexual differentiation of the vertebrate nervous system

Abstract: The steps leading to masculinization of the body are remarkably consistent across mammals: the paternally contributed Y chromosome contains the sex-determining region of the Y (Sry) gene, which induces the undifferentiated gonads to form as testes (rather than ovaries). The testes then secrete hormones to masculinize the rest of the body. Two of these masculinizing testicular hormones are antimullerian hormone, a protein that suppresses female reproductive tract development, and testosterone, a steroid that promotes development of the male reproductive tract and masculine external genitalia. In masculinizing the body, testosterone first binds to the androgen receptor protein, and then this steroid-receptor complex binds to DNA, where it modulates gene expression and promotes differentiation as a male. If the Sry gene is absent (as in females, who receive an X chromosome from the father), the gonad develops as an ovary, and the body, unexposed to testicular hormones, forms a feminine configuration. The genitalia will only respond to testicular hormones during a particular time in development, which constitutes a sensitive period for hormone action: hormonal treatment of females in adulthood has negligible effects on genital morphology 1 . Of the two gonadal hormones that masculinize the body, it is testosterone that also masculinizes the brain. Scientists first demonstrated this by exposing female guinea pigs to testosterone in utero ,w hich permanently interfered with the animals’ tendency to show female reproductive behaviors in adulthood 2 .T reating adult females with testosterone had a transient effect, or none at all, on these behaviors. Early exposure to steroids such as testosterone also masculinizes brain structures. In this review, we will contrast the various mechanisms by which testosterone masculinizes the central nervous system, discuss the unknowns that remain and relate these findings to human behavior.

Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system.

Abstract: To determine whether insulin stimulates human ovarian testosterone production in the polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system, thecal cells from polycystic ovary syndrome women were isolated and cultured. Insulin and insulin-like growth factor I stimulated thecal testosterone biosynthesis. Antibody blockade of the insulin receptor abolished insulin's stimulatory action, whereas effective antibody blockade of the insulin-like growth factor I receptor did not alter insulin's stimulation of thecal testosterone biosynthesis. A chiro-inositol containing glycan (INS-2) increased thecal testosterone biosynthesis. Preincubation of cells with an antiinositolglycan antibody (A23939 or alpha IGP) abolished insulin's stimulatory effect, but not that of hCG. These findings suggest that inositolglycans serve as the signal transduction system for insulin's stimulation of human thecal testosterone biosynthesis.