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.
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TL;DR: Discontinuation of flutamide was associated with a significant decrease in PSA values in 10 of 25 patients and clinical improvement in a subset of patients who had an initial response, but later progressive disease on combined androgen blockade.
Abstract: PURPOSETo evaluate the effect of discontinuation of the antiandrogen, flutamide, in patients with metastatic prostate cancer who are progressing on hormonal therapy.PATIENTS AND METHODSThirty-six patients with progressive disease on hormonal treatment that included flutamide had discontinuation of the antiandrogen. Thirty-five (95%) had progressive increases in prostate-specific antigen (PSA) levels, despite castrate levels of testosterone. Twenty-five patients (69%) were treated with combined androgen blockade (orchiectomy or gonadotropin-releasing hormone [GnRH] analog plus flutamide) as initial therapy and 11 (31%) were started on monotherapy alone. Patients who had not undergone a previous orchiectomy were continued on the GnRH analog. Patients were monitored clinically and with serial PSA measurements, radionuclide scans, and radiographs as indicated to assess response.RESULTSConsidering the 35 patients with increasing PSA values, 10 (29%) showed a significant decline (> or = 80% in seven, and > or =...
399 citations
TL;DR: It is demonstrated that immune cells in the brain interact with the nervous and endocrine systems during development, and are crucial for sexual differentiation of brain and behavior, and the mechanisms underlying this feedforward process were unknown.
Abstract: Brain sexual differentiation in rodents results from the perinatal testicular androgen surge. In the preoptic area (POA), estradiol aromatized from testosterone upregulates the production of the proinflammatory molecule, prostaglandin E2 (PGE2) to produce sex-specific brain development. PGE2 produces a two-fold greater density of dendritic spines in males than in females and masculinizes adult copulatory behavior. One neonatal dose of PGE2 masculinizes the POA and behavior, and simultaneous treatment with an inhibitor of additional prostaglandin synthesis prevents this masculinization, indicating a positive feedforward process that leads to sustained increases in PGE2. The mechanisms underlying this feedforward process were unknown. Microglia, the primary immunocompetent cells in the brain, are active neonatally, contribute to normal brain development, and both produce and respond to prostaglandins. We investigated whether there are sex differences in microglia in the POA and whether they influence developmental masculinization. Neonatal males had twice as many ameboid microglia as females and a more activated morphological profile, and both estradiol and PGE2 masculinized microglial number and morphology in females. Microglial inhibition during the critical period for sexual differentiation prevented sex differences in microglia, estradiol-induced masculinization of dendritic spine density, and adult copulatory behavior. Microglial inhibition also prevented the estradiol-induced upregulation of PGE2, indicating that microglia are essential to the feedforward process through which estradiol upregulates prostaglandin production. These studies demonstrate that immune cells in the brain interact with the nervous and endocrine systems during development, and are crucial for sexual differentiation of brain and behavior.
399 citations
TL;DR: Androgen receptors are present in cardiac myocytes from multiple species, including normal men and women, in a context that permits androgens to modulate the cardiac phenotype and produce hypertrophy by direct, receptor-specific mechanisms.
Abstract: Background—The role of androgens in producing cardiac hypertrophy by direct action on cardiac myocytes is uncertain. Accordingly, we tested the hypothesis that cardiac myocytes in adult men and women express an androgen receptor gene and that myocytes respond to androgens by a hypertrophic response. Methods and Results—We used reverse transcription–polymerase chain reaction methods to demonstrate androgen receptor transcripts in multiple tissues and [3H]phenylalanine incorporation and atrial natriuretic peptide secretion as markers of hypertrophy in cultured rat myocytes. Messenger RNA encoding androgen receptors was detected in myocytes of male and female adult rats, neonatal rat myocytes, rat heart, dog heart, and infant and adult human heart. Both testosterone and dihydrotestosterone produced a robust receptor-specific hypertrophic response in myocytes, determined by indices of protein synthesis and atrial natriuretic peptide secretion. Conclusions—Androgen receptors are present in cardiac myocytes fro...
396 citations
TL;DR: The results suggest that continuous exposure to medium levels of estrogens, particularly in the presence of sustained low progesterone secretion, may alter pituitary secretion of prolactin in aging rats.
Abstract: Longitudinal studies were performed in a colony of aging female rats,from 4-33 months of age,to determine the chronologicalchange inreproductive patterns and the changes in sex steroid, prolactin and gonadotropin secretionassociatedwith different reproductive states. The present study demonstrates that the incidence (65%) of irregular estrous cycles in aging rats increased abruptly from 10-12 months of age. Subsequently, female rats became chronically anovulatory with persistentvaginalcornificationsand theirovariescontained developed follicles but no corpora lutea. The highest incidence (65%) of constant estrous (CE) rats occurred at the age of about 19 months. During the anovulatory state, CE rats displayed low to medium levels of serum estradiol, estrone, testosterone and androstenedione, low levels of progesterone and minimal levels of 20nhydroxyprogesterone. Preovulatory increasesin gonadotropin and prolactin release,similar to those seen in young cycling ratson proestrus,were not observed in CE rats.Whereas serum basal LH levels remained unaltered, morning FSH levelswere increased in CE rats.The lattermay account for the persistent follicular development in aging rats during chronic anovulatory state. Serum basal prolactin levels were normal in CE rats during the early phase (11-16 months of age) of the anovulatory state, but were subsequently increased 3 to 4-fold beyond 24 months of age. Moreover, ovariectomy at a young age prevented the increased pituitary prolactin release in old female rats. These results suggest that continuous exposure to medium levels of estrogens, particularly in the presence of sustained low progesterone secretion, may alter pituitary secretion of prolactin in aging rats. With further advance of age and following many months of anovulatory function, aging female rats exhibited ovulatory activity at irregular intervals. After each ovulation, formed corpora lutea were maintained for a prolonged period, presumably due in part to the existing high prolactin levels in the circulation of older female rats. These corpora lutea in old “pseudopregnant (PSP)” rats were functional as indicated by active secretion of progestins, with 20a-hydroxyprogesterone levels greater than those of progesterone in the circulation. These results indicate that the ovaries of aging rats retain their functional capacity to develop follicles and corpora lutea and to secrete steroid hormones. Although the cause(s) responsible for cessation of normal ovulatory cycles in aging female rats is unknown, the present study demonstrates that the chronic anovulatory state in aging female rats is characterized by significantly reduced ovarian secretion and the lack of cyclic increases in pituitary gonadotropin and prolactmn release. The causal relationships between the decreased ovarian steroid production and the absence of preovulatory surges of gonadotropin release in aging CE rats remain to be determined.
396 citations
TL;DR: This particular form of drug abuse stems from the convergence of several separate misconceptions about the effects of androgen misuse on muscle mass and lean body weight.
Abstract: Introduction ANDROGEN abuse by athletes constitutes only a portion of the problem of androgen misuse by the general population (1) and only a minor aspect of the doping of athletes with drugs presumed to enhance athletic ability (2, 3). Indeed, of the drugs banned by the International Olympic Committee, steroids account only for about 15% (4). This particular form of drug abuse stems from the convergence of several separate misconceptions. The first was the recognition that the administration of androgens to hypogonadal males causes an increase in nitrogen retention and an increase in muscle mass and lean body weight (5). It followed that the differences in muscle mass between men and women are largely due to differences in testosterone levels, and it was assumed that the administration of androgens in supraphysiological amounts to normal men would do even more than the normal amount. The second misconception was that the anabolic (muscle promoting) and androgenic (virilizing) actions of the hormone are e...
395 citations