Hypogonadism and feminization in the male: a triple effect of alcohol.
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Alcoholism↗
Biomedical subjects
G G Gordon
Publications and source records attributed to G G Gordon.
Cellular regulation of the metabolism of androgens in rat oral mucosa. II. Product activation of 17 beta-hydroxysteroid oxidoreductase enzyme system.
Product activation of 17beta-hydroxysteroid oxidoreductase for testosterone and androstenedione was established using the enzyme preparation from rat oral mucosa. It is suggested that this activation could be due to the conformational changes of the enzyme.
17-Hydroxysteroid Dehydrogenases↗
Cellular regulation of the metabolism of androgens in rat oral mucosa. III. Activation of delta 4-3-ketosteroid-5alpha-A ring reductase enzyme system by 5,5-diphenylhydantoin.
Systemic pretreatment of rats with diphenylhydantoin (DPH) or its addition into an in vitro assay increases 5alpha-reduction of testosterone by the oral mucosa. Enzyme kinetic studies showed that DPH binds to the enzyme and probably activates it by an allosteric mechanism.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Concentration of circulating hormones and metabolism of androgens by human gingiva.
The present study evaluates the relationship between periodontal status, concentration of circulating hormones and metabolism of androgens by human male and female gingiva in vitro. In both male and female patients with healthy gingiva the plasma concentration of gonadotropins (LH and FSH) and steroid hormones (testosterone, androstenedione, estradiol-17 beta, progesterone and cortisol) were in a normal range. However, an alteration in the plasma concentration of progesterone was found in both male and female patients with periodontal pathosis. Both androgens (testosterone and androstenedione) were readily metabolized by human gingiva tissue in vitro. The major pathway of the metabolism of testosterone was via the formation of 17 beta-hydroxy-5 alpha-A-ring reduced androgens (5 alpha-dihydrotestosterone and 3 alpha-, 3 beta-androstanediol). In contrast, androstenedione was metabolized mainly to 17-keto-5 alpha-A-ring reduced (5 alpha-androstanedione, androsterone and epiandrosterone) and 17 beta-oxidoreduced (testosterone) compounds. In addition both substrates were metabolized to 5 beta-A-ring reduced androgens (5 beta-dihydrotestosterone, 5 beta-androstanediol and 5 beta-androstanedione). A significant feature of the metabolism of testosterone and androstenedione by inflamed gingiva was an increase of 5 alpha-A-ring reductase activity (mainly the formation of 5 alpha-dihydrotestosterone and 5 alpha-androstanedione) and 17 beta-oxidoreductase activity (mainly the formation of testosterone from androstenedione). The increase in 5 alpha-reductase activity also showed a significant correlation with the plasma progesterone concentration.
Adolescent↗
Effect of chronic alcohol use on hepatic testosterone 5-alpha-A-ring reductase in the baboon and in the human being.
Hepatic testosterone 5-alpha-A-ring reductase (HTAR) activity was measured in open liver biopsies in eight alcohol-fed baboons and eight pair-fed controls. The animals were studied after at least 1 yr of alcohol feeding. In the alcholol-fed animals, a significant fall in enzyme activity was noted. This occurred whether the enzyme levels were related to soluble protein, to DNA, or to wet tissue weight, showing that the change was due to a decrease in the specific activity of the enzyme. In addition, aspiration liver biopsy specimens were obtained from 14 men and women with alcoholic liver disease. Again, there was a significant decrease in HTAH activity in these patients compared with a normal population. No relationship was found between hepatic histology and HTAR levels in either the baboon or human population with alcoholic liver disease, suggesting that the changes in enzyme activity were related to an alcohol effect rather than to liver disease per se. This study demonstrates that chronic alcohol use decreases the function of the enzyme which controls an important rate-limiting step in the metabolism of testosterone in the liver and that this effect may be due primarily to alcohol.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Nuclear translocation of the cytoplasmic glucocorticoid receptor in the iris--ciliary body of the rabbit.
The cytoplasmic glucocorticoid receptor of the iris--ciliary body of the rabbit has been shown to translocate to the cell nucleus within 30 min of an injection of cortisol. Over the next 2 1/2 hr the amount of receptor returns to the control value. The threshold of the loss of receptor from the cytosol was found at 0.04 mg of cortisol per kilogram body weight, with a maximal loss being reached at a cortisol dose of 0.5 mg/kg B.W. The inactive glucocorticoid tetrahydrocortisol and the major sex steroids, dihydrotestosterone, estradiol, and progesterone, had little or no effect on this translocation, indicating the specificity of the cortisol effect. Thus this receptor appears to migrate to the cell nucleus in a manner similar to that found in other steroid-sensitive tissues and is consistent with the accepted mechanism whereby these hormones regulate differential gene expression in the nucleus.
Animals↗
Receptors for glucocorticoids in the lens epithelium of the calf.
The calf lens epithelium contains a specific cytoplasmic receptor for glucocorticoids. This binding protein has a high affinity for dexamethasone (average dissociation constant, 8 x 10(-9) mole per liter), a low capacity (average, 550 femtomoles per milligram of protein), extreme heat sensitivity, and exhibits a pattern of competition similar to that of glucocorticoid receptors in other tissues. This provides direct biochemical evidence that these tissues may function as a target organ for glucocorticoids.
Animals↗
The effects of alcoholic liver disease and alcohol ingestion on sex hormone levels.
This study showed that alcohol significantly decreases plasma testosterone levels, with changes noted as early as the first day of alcohol use (loss of pulsatile secretion). This effect is due, in part, to a direct testicular action since it occurred without LH suppression and in the presence of elevated LH levels. More chronic use of alcohol resulted in a suppression of LH. Thus, alcohol use in nonalcoholic men is associated with an effect both at the testicular and hypothalamic-pituitary levels.
Animals↗
Effect of progestins on androgen delta4-3-ketosteroid-5alpha-A-ring reductase system in rat oral mucosa.
Rat oral mucosa microsomal delta4-3-ketosteroid-5alpha-A-ring reductase enzyme system, reducing testosterone and 4-androstenedione, was found to be inducible by systemic administration of medroxyprogesterone acetate (MPA). MPA, when used in a mixture with testosterone and/or 4-androstenedione in vitro, acted as a competitive inhibitor of the reduction of these substrates.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Specific 5 alpha-dihydrotestosterone receptors in human gingiva.
The cytoplasm of normal human male and female gingiva contains a receptor capable of specifically binding 5 alpha-dihydrotestosterone (DHT). This binding has a high affinity for DHT (Kd, approximately 2.2 x 10-9 M) and a low capacity (approximately 190 fmol/mg protein). The binding is extremely heat sensitive and exhibits a pattern of competition similar to that obtained with DHT receptors from other target tissues. The demonstration of a specific DHT receptor in human gingiva provides the first direct biochemical evidence that this tissue may function as a target organ for androgens. There was no correlation between the Kd in normal tissue and gingival hyperplasia or between the Kd or number of binding sites and the age or sex of the patient. However, there sites and the age or sex of the patient. However, there was a significant difference (P less than 0.0005) between the amount of DHT-binding sites per mg protein in normal tissue as compared to gingival hyperplasia (drugs or pregnancy).
Adolescent↗
Androstenedione metabolism in patients with endometrial cancer.
The plasma concentration of androstenedione and the instantaneous conversion of androstenedione to estrone was increased in patients with endometrial cancer as compared to postmenopausal control subjects. Moreover, the per cent of estrone derived from androstenedione was increased in the cancer group.
Androstenedione↗
Thyroid - hormone effects on steroid - hormone metabolism.
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Animals↗
Specific glucocorticoid receptor in the iris--ciliary body of the rabbit.
The cytoplasm of the iris--ciliary body of the rabbit contains a receptor capable of specifically binding dexamethasone. This binding protein has a high affinity for dexamethasone (average KD = 2.0 X 10(-8) M), a low capacity (average 4.8 X 10(-13) mol of steroid bound per milligram of protein), and extreme heat sensitivity; it exhibits a pattern of competition virtually identical to that obtained with glucocorticoid receptors from other tissues and shows characteristic physicochemical behavior in various salt concentrations. The demonstration of a specific dexamethasone receptor in the iris--ciliary body provides the first direct biochemical evidence that these tissues may function as a target organ for glucocorticoids.
Animals↗
Effect of alcohol (ethanol) administration on sex-hormone metabolism in normal men.
To determine whether ethanol per se affects testosterone metabolism, alcohol was administered to normal male volunteers for periods up to four weeks, resulting in an initial dampening of the episodic bursts of testosterone secretion followed by decreases in both the mean plasma concentration and the production rate of testosterone. The volunteers received adequate nutrition and none lost weight during the study, which tended to exclude a nutritional disturbance as the cause of the decreased testosterone levels. The changes in plasma luteinizing hormone suggested both a central (hypothalamus-pituitary) and gonadal effect of alcohol. In addition, alcohol consumption increased the metabolic clearance rate of testosterone in most subjects studied, probably owing to the combined effects of a decreased plasma binding capacity for the androgen and increased hepatic testosterone A-ring reductase activity. These results indicate that alcohol markedly affects testosterone metabolism independently of cirrhosis or nutritional factors.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Prolonged ethanol consumption increases testosterone metabolism in the liver.
Male alcoholics often suffer from features of hypogonadism related to abnormal metabolism of sex steroids. Since the activity of testosterone reductases is rate limiting for testosterone metabolism in the liver, the effect of prolonged ethanol consumption by rats and human volunteers on the activities of these microsomal and cytosolic enzymes was studied. In rats, long-term ethanol ingestion doubled microsomal 5alpha-testosterone reductase activity, a major pathway for testosterone metabolism, while in human volunteers the activity was increased two- to fivefold. These changes may play a role in the altered androgenic activity of the chronic alcoholic.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Testosterone metabolism in endometrial cancer.
Plasma testosterone (PCT), metabolic clearance (MCRT), and production rates (PRT) of testosterone and conversion ratio of testosterone to androstenedione (CRppTA) were performed on 11 patients with endometrial cancer and on a control group of five postmenopausal women. The PCT, MCRT, and PRT of patients with endometrial cancer are in the normal postmenopausal range. The conversion of testosterone to androstenedione in patients with endometrial cancer was significantly decreased.
Aged↗
Steroid metabolism in ocular tissues of the rabbit.
The metabolism of cortisol and other steroids was studied in normal untreated rabbit iris-ciliary body and cornea as part of an investigation into the mechanism of glucocorticoid-induced glaucoma. Cortisol is readily converted to the inactive metabolite cortisone by these eye tissues indicating the presence of an 11beta-oxidoreductase system. This reaction is reversible with cortisone being converted to cortisol in the presence of appropriate cofactor. However, due to the absence of a (or as yet undetectable) cortisol-A-ring-reductase system (rate-limiting reaction) the steroid is not irreversibly metabolized to biologically inactive compounds. The 11beta-oxidoreductase system readily converts other C21-11beta-hydroxysteroids, such as corticosterone, to its appropriate C21-11-ketosteroid (11-dehydrocorticosterone). Some C21-steroids lacking the 11-hydroxyl group (11-deoxycortisol, 11-deoxycorticosterone) remain virtually unmetabolized (exception to this was found with progesterone). Evidence of a C21-steroid A-ring reductase system was found only when cortisone and progesterone were used as substrates. However, testosterone a C19 steroid was converted to clearly identifiable A-ring reduced and 17beta-and 3alpha(beta)-oxidoreduced metabolites, thus indicating the presence of testosterone A-ring reductase, 17beta-and 3alpha(beta)-oxidoreductase systems in the eye tissues studied. The presence of a steroid 5alpha(beta)-reductase for some steroids but not for cortisol indicates a distinct substrate specificity for this enzyme system in the eye tissues.
Androstenedione↗
Rhythms and testosterone metabolism.
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3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗