Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies in this laboratory have described an unusual kindred in which gynecomastia resulted from abnormally elevated levels of extraglandular aromatase activity. In order to better understand the molecular mechanisms responsible for the abnormal aromatase activity in these and other patients, we explored the aromatase activity of genital skin fibroblasts. Our studies demonstrate that the kinetic parameters for aromatase in skin are similar to those of other cultured cells and suggest that skin is an important site of extraglandular aromatase activity. These cells also contain 5 alpha-reductase activity and androgen receptors and are, therefore, a model for androgen action and metabolism. For example, they provided a system for the study of the potency and specificity of the aromatase inhibitors 4-OHA and MDL 18,962. Finally, the influence of DEX on aromatase in genital skin fibroblasts differs in some important respects from the pattern of control observed in adipose tissue stromal-vascular cells. These findings suggest that investigating the molecular mechanisms for the regulation of aromatase in skin may provide unique information about the control of the enzyme.
Steroids
PMID:Aromatase activity in human skin fibroblasts grown in cell culture. 350 63

The title compound was synthesized as part of an effort to determine the identity of an abnormal steroid metabolite present in the urine of a patient exhibiting pronounced gynecomastia. The X-ray investigation of the synthesized compound showed that the 20-carbonyl of the 17 alpha oriented side chain lies under the D ring, and does not participate in hydrogen bonding in the crystal lattice. This conformation appears to be stable and sufficiently shielded that it is unlikely to make a major contribution to possible protein interactions.
Steroids
PMID:Structure determination of 3 beta, 17-dihydroxy-17 alpha-pregn-5-ene-20-one. 383 52

We report a 14 year-old male with severe, long-lasting gynecomastia. Baseline serum androstenedione levels were elevated compared to testosterone levels (330 ng/dl vs 28 ng/dl). In order to evaluate testosterone biosynthesis by this patient in more detail, androstenedione, testosterone, dehydroepiandrosterone (DHEA) and estradiol responses to a single dose of hCG were measured. The responses observed were different from those reported in normal males in two respects: 1) there was no immediate rise in testosterone two to four hours after the injection of hCG, and 2) levels of androstenedione and estradiol at 24, 36 and 48 hours after injection were much higher than expected. We postulate that a partial defect in testicular 17-ketosteroid reductase activity was responsible for the abnormal androstenedione to testosterone ratio in our patient. This, in turn, lead to an increased peripheral synthesis of estrogens and marked gynecomastia.
Steroids 1985 Feb
PMID:Partial deficiency in 17-ketosteroid reductase presenting as gynecomastia. 386 88

Incubation studies have been carried out using normal breast tissue and breast tissue from patients with gynecomastia, mammary dysplasia and breast carcinoma to determine the pattern of androstenedione metabolism. All tissues formed estrone (E1) and testosterone (T) in all incubations. Estradiol (E2) was isolated in incubations of tissue from 1 of 6 patients with mammary dysplasia, 5 of 6 patients with gynecomastia and in all incubations with normal and carcinoma tissue. Estrone formation was lowest in mammary dysplasia and gynecomastia, and higher in apparently normal breast tissue. The greatest E1 formation was found in incubations with breast carcinoma tissue, although there was considerable variation within this tissue group. Estradiol formation was low in all tissues, with the highest conversion rates in carcinoma tissue. Testosterone formation in carcinoma tissue was greater than in mammary dysplasia or gynecomastia, but similar to apparently normal tissue. These results indicate that breast tissue from different pathological states varies in its capacity to aromatize androstenedione (A) to estrogenic products and to convert it to other androgens. They have also shown that the pattern of metabolism is distinctive for the nature of the pathological abnormality.
Steroids 1981 Mar
PMID:Androgen metabolism in male and female breast tissue. 723 57

Gynaecomastia is a common and well-recognised side-effect of anabolic steroid abuse in athletes. A staging system is proposed and a technique of excision under local anaesthetic described. Careful selection of cases and the use of meticulous technique can achieve good cosmetic results, without risk of recurrence of gynaecomastia.
 ...
PMID:Surgical correction of gynaecomastia in bodybuilders. 754 53

A study of a large cell calcifying Sertoli cell tumor of the testis associated with bilateral gynecomastia in an 8-year-old boy is presented. Macroscopically, the two testes showed multiple, large, and hard calcified nodules. Histology revealed clusters or cords of tumor cells with foci of calcifications as well as evidences, in the adjacent testicular parenchyma, of initiation of gonadal development, such as early signs of spermatogenesis and sparse Leydig cell differentiation. In vivo, serum hormone studies showed gonadotropin-independent gonadal activity. After orchidectomy two macroscopically distinct fractions of the removed testes, tumoral and extratumoral, were processed separately for cell isolation and culture. The secretion of testosterone, androstenedione, and 17-hydroxyprogesterone to the medium on day 6 of culture showed that steroidogenesis in cells of the extratumoral fraction was more active than in the tumoral fraction. On the other hand, tumoral fraction cells showed much higher aromatase activity than extratumoral cells. Furthermore, conditioned medium of tumoral fraction cells was able to stimulate testosterone secretion when it was added to subcultures of testicular cells isolated from a control subject. It is postulated that tumoral cells might have stimulated neighboring interstitial cells to differentiate into Leydig cells and to secrete androgens, which in turn might have been aromatized to estrogens by tumoral cells.
Steroids 1995 Feb
PMID:Testicular steroid biosynthesis in a boy with a large cell calcifying Sertoli cell tumor producing prepubertal gynecomastia. 761 89

Recognition of the pathogenesis of secondary forms of hypertension is often considered the key to appropriate choice of treatment. We here present the results of a prolonged clinical follow-up (from 1 to 20 years) of a large number of patients with mineralocorticoid excess syndromes (MES), including over 100 patients with primary aldosteronism (PA), 3 cases with dexamethasone-suppressible aldosteronism (DSA), 3 cases of apparent mineralocorticoid excess (AME) Type II, and 4 patients with 17-hydroxylase deficiency (17OHDS). The patients with PA have been divided in two subgroups, one of 69 cases followed between 1973 and 1982, and the second of 37 patients studied between 1983 and 1992; 33 further cases were not evaluated due to poor compliance. In group I, 26 patients underwent surgery (23 unilateral adenoma, 1 primary hyperplasia, 2 bilateral nodular hyperplasia); at 5 years 50% had normal blood pressure, 25% had mild hypertension and 25% had moderate to severe hypertension. Forty-three patients with either adenoma (APA) or idiopathic aldosteronism (IHA) received long-term spironolactone treatment. Among them, 13 required the addition of thiazide and/or beta-blockers, while 13 were switched to an amiloride/thiazide combination (+/- beta blockers) due to side-effects to spironolactone (gynecomastia 6/20 males, menstrual upset or breast pain in 7/23 females). In group II, 12 patients underwent surgery (11 adenoma, 1 primary hyperplasia) with a similar outcome at 3 years as in group I; 25 patients were put on either K canrenoate (11) or Ca++ channel blockers (14) with or without KCl supplementation; in 8 cases these two drugs were combined according to blood pressure levels achieved during the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1995 Jan
PMID:Long-term treatment of mineralocorticoid excess syndromes. 779 22

Male sexual differentiation and development proceed under direct control of androgens. Androgen action is mediated by the intracellular androgen receptor, which belongs to the superfamily of ligand-dependent transcription factors. In the X-linked androgen insensitivity syndrome, defects in the androgen receptor gene have prevented the normal development of both internal and external male structures in 46, XY individuals. The complete form of androgen insensitivity syndrome is characterized by 46, XY karyotype, external female phenotype, intra-abdominal testes, absence of uterus and ovaries, blindly ending vagina, and gynecomastia. There is also a group of disorders of androgen action that result from partial impairment of androgen receptor function. Clinical indications can be abnormal sexual development of individuals with a predominant male phenotype with severe hypospadias and micropenis or of individuals with a predominantly female phenotype with cliteromegaly, ambiguous genitalia, and gynecomastia. Complete or gross deletions of the androgen receptor gene have not been frequently found in persons with the complete androgen insensitivity syndrome, whereas point mutations at several different sites in exons 2-8 encoding the DNA- and androgen-binding domain have been reported in both partial and complete forms of androgen insensitivity, with a relatively high number of mutations in two clusters in exons 5 and 7. The number of mutations in exon 1 is extremely low, and no mutations have been reported in the hinge region, located between the DNA-binding domain and the ligand-binding domain. The X-linked condition of spinal and bulbar muscle atrophy (Kennedy's disease) is characterized by a progressive motor neuron degeneration associated with signs of androgen insensitivity and infertility. The molecular cause of spinal and bulbar muscle atrophy is an expanded length (> 40 residues) of one of the polyglutamine stretches in the N-terminal domain of the androgen receptor.
Steroids 1996 Apr
PMID:Molecular basis of androgen insensitivity. 873 95

Anabolic androgenic steroids (AS) have recently been placed on the Food and Drug Administration's (FDA's) list of controlled substances, because of the adverse effects seen in athletes taking accelerated dosages in attempts to enhance performance. Reported deleterious effects on abusers include sterility, gynecomastia in males, acne, balding, psychological changes, and increased risks of heart disease and liver neoplasia. Considering the roles of the immune and neuroendocrine systems and their interactions in many of these pathologies, it is important to determine the effects of these derivitized androgens on this connection. Little is known in this respect. We therefore determined the effects of anabolic steroids on certain immune responses and their effects on the extrapituitary production of corticotropin by lymphocytes. We present evidence that (1) both 17-beta and 17-alpha esterified AS, nandrolone decanoate and oxymethenelone, respectively, significantly inhibited production of antibody to sheep red blood cells in a murine abuse model; (2) the control androgens testosterone and dehydroepian-drosterone (DHEA) or sesame seed oil vehicle had no significant effects on antibody production; (3) nandrolone decanoate and oxymethenelone directly induced the production of the inflammatory cytokines IL-1 beta and TNF-alpha from human peripheral blood lymphocytes but had no effect on IL-2 or IL-10 production; (4) control androgens had no direct cytokine inducing effect; (5) nandrolone decanoate significantly inhibited IFN production in human WISH and murine L-929 cells; and (6) nandrolone decanoate significantly inhibited the production of corticotropin in human peripheral blood lymphocytes following viral infection. These data indicate that high doses of anabolic steroids can have significant effects on immune responses and extrapituitary production of corticotropin. Furthermore, the mouse model should provide an effective means by which to study other deleterious effects of anabolic steroid abuse in humans.
 ...
PMID:Modulation of immune responses by anabolic androgenic steroids. 878 15

The main groups of drugs that affect male libido, potency, sperm production, structure and function are summarized and their mechanisms described when known. About 15% of the 200 most commonly prescribed drugs can have adverse effects on male reproduction. Sedatives, tranquilizers, hypnotics, antiandrogens and the common antihypertensive methyldopa can depress libido. Spironoacetone has been reported to impair libido, potency, sperm count and motility, although reversibly. The phenothiazines and tricyclic antidepressants may induce prolactin secretion and consequent gynecomastia. Narcotics and hallucinogens influence male sexual performance. Morphine and methadone decrease LH and testosterone, and increase prolactin. Cannabis, hashish and marijuana initially increase libido and potency, but chronic use causes sexual inversion. Chronic alcoholism also may upset testosterone metabolism, causing testicular atrophy. Cyclophosphamide, used for nephrotic syndrome, and nitrofurans, used as food preservatives, cause direct damage to seminiferous tubules. Synthetic oganochlorine pesticides, especially DDT, have also been reported to damage spermatogenic cells directly, when injected in mice. Steroids such as ACTH, hydrocortisone and dexamethasone may inhibit steroidogenesis in animals.
 ...
PMID:Effect of pharmacological agents on male reproduction. 1234 6


1 2 Next >>