Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00627 (MAP)
 15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The androgenic action of dihydrotestosterone (DHT) is antagonized by agents that compete with testosterone for the 5 alpha-reductase enzyme and by agents that block the binding of DHT to its receptor. The topical synergistic effect of 5 alpha-reductase (5 alpha RI) and androgen receptor inhibitors (ARI) was determined by measurement of the sebaceous gland size (SGS) of the ventral ear skin of the intact, sexually mature male Syrian hamsters. Progesterone (P), a 5 alpha RI, and spironolactone (SL), an ARI, produced a dose responsive decrease in SGS at topical concentrations of 0.01% to 5.0%. At concentrations of 1, 3, and 5%, P and SL combinations produced neither an additive nor synergistic inhibition of SGS. At very low concentrations of up to 0.10%, neither P nor SL alone produced any effect on SGS. When combinations of these two steroids were applied at low concentrations, SGS decreased unilaterally to approximately 50%. This synergy occurred best at a P:SL ratio of 1:2. The lower effective concentrations of P may be explained by its greater percutaneous absorption. Synergy was also demonstrated at low concentrations with other antiandrogens: cyproterone acetate, canrenone, hydroxyflutamide, and N-N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane- 17 beta-carboxamide. The use of anti-androgen combinations at low concentrations is of value because of the decreased risk of systemic side effects while maintaining potent topical efficacy.
J Invest Dermatol 1988 Nov
PMID:Synergistic antiandrogenic effects of topical combinations of 5 alpha-reductase and androgen receptor inhibitors in the hamster sebaceous glands. 317 Dec 18

The androgen status of a hirsute woman can be diagnosed today by new techniques for measuring circulating androgens. Unfortunately, a battery of expensive tests is required to make this assessment. Two specific basic screening tests, DHEA-S and total free testosterone determinations, should be done. If the patient is interested in and can afford it, further testing can be done; it includes 17-hydroxyprogesterone, prolactin, compound S (serum 11-deoxycortisol) and cortisol measurements and a dexamethasone suppression test. Elevations of androgens, whereas elevations of testosterone can be due to ovarian or adrenal secretion. Establishing the site of androgen hypersecretion allows one to be more selective regarding the antiandrogen therapy. When excess androgen secretion is primarily adrenal in origin, adrenal suppression is effective with the use of such drugs as dexamethasone. If the excess androgen is primarily of ovarian origin, cyclic estrogens, for example, Demulen or Premarin with Provera, would be helpful. The evaluation of a hirsute patient takes time, interest, and knowledge of specific androgen-dependent cutaneous syndromes involving multiple possible enzymatic defects in the conversion of cholesterol to testosterone or intercellular pathways of androgen metabolism. If the dermatologist is not interested in or lacks the knowledge for such an evaluation, the patient is best referred to an interested endocrinologist.
Dermatol Clin 1987 Jul
PMID:Hirsutism. 330 Nov 8

Women at risk of pregnancy who are using potentially teratogenic drugs need to be provided with a highly effective method of contraception. For purposes of contraceptive planning, these women should be asked if they would seek an abortion should conception accidentally occur. If abortion is acceptable, use of any contraceptive seems reasonable. On the other hand, women who would not consider abortion must be provided with a fail-safe method of fertility control. A present, only 3 contraceptives fit this description: depomedroxyprogesterone acetate, oral contraceptives, and intrauterine devices. Oral contraceptives are the most popular method among younger women, and their use-effectiveness rate is high when women are motivated by a fear of adverse obstetric outcomes. Intrauterine methods are usually inappropriate for women who have not completed childbearing and are less well tolerated by nulligravid women than women with prior pregnancies. Depomedroxyprogesterone acetate may be the method of choice for selected young women who cannot tolerate the pill or cannot remember to take it. To further decrease the likelihood of unwanted pregnancy, condom use should be encouraged for the sexual partners of women at high risk of fetal anomalies and for whom abortion is not acceptable.
J Am Acad Dermatol 1987 Jul
PMID:Reversible contraception for women at high risk of fetal anomalies. 361 51

The antimitotic activity of oxidized derivatives of cholesterol was investigated using an assay developed by Van Scott and Bonder. In this assay, a drug that has antimitotic activity and is not a metaphase-blocking agent will inhibit the formation of podophyllin-induced metaphase figures, as counted on histologic specimens. Mouse vaginal epithelia were classified as being estrogen or progesterone predominant on the basis of histologic criteria. Podophyllin-injected mice in the estrogenic phase of the estrus cycle demonstrated high metaphase-figure counts, with an average of 284.86 +/- 132.01. In this group, all intravaginally administered compounds, inhibited the formation of metaphase figures, including a propylene-glycol ethanol vehicle (60% suppression); thus, it is concluded that animals in this phase are not a suitable model for assaying antimitotic activity. Mice in the progesterone-predominant phase of the estrus cycle had lower counts of podophyllin-induced metaphase figures, i.e., 142.13 +/- 39.29. In this group, 25-OH-cholesterol was the most effective inhibitor (59% suppression), followed by 7-ketocholesterol (48% suppression) and methotrexate (40% suppression). Cholesterol (5% suppression) and vehicle (20% suppression) did not have any significant effects. Progesterone-predominant epithelium was only susceptible to methotrexate and oxidized sterols. This suggests that oxidized sterols may have antimitotic activity.
Arch Dermatol Res 1985
PMID:Oxidized sterols inhibit the formation of podophyllin-induced metaphase figures in mouse vaginal epithelia. 405 57

Cytosol of cultured human epidermal keratinocytes contains macromolecules, that bind corticoids with high affinity. Binding constants were in the same range for cultured keratinocytes originating from different individuals and did not change during serial cell cultivation. At 0 degree C and using 3H-triamcinolone acetonide as ligand, we obtained the following values; apparent Bmax = 160- 250 fmoles/mg protein and Kdiss = 3.1-5.0 nM; with 3H-dexamethasone Bmax = 200-350 fmoles/mg protein, Kdiss = 6.0-11.1 nM, and with 3H-hydrocortisone Bmax = 140-220 fmoles/mg protein, Kdiss = 17-25 nM. There was an indication that the binding capacity of the receptor system is higher the younger the age of the skin donor. A number of steroids and corticoids commonly used in dermatological practice were tested with respect to displacement of 3H-triamcinolone acetonide, 3H-dexamethasone, and 3H-hydrocortisone from binding sites in cytosol. Good correlation between clinical efficacy and specific binding was observed for all 3 ligands. Other steroids such as 17-beta estradiol and nandrolone did not show any affinity for the corticoid binding system. Progesterone displace 3H-corticoids from their binding sites, but the IC50 was of one order of magnitude larger.
J Invest Dermatol 1981 Mar
PMID:Corticoids and cultured human epidermal keratinocytes: specific intracellular binding and clinical efficacy. 616 79

The effect of progesterone on 14C-testosterone metabolism and on 14C-lipid synthesis was studied in two animal sebaceous gland models, hamster flank organ and rat ear skin. Unilateral topical application of progesterone to the female hamster flank organ topically treated with testosterone propionate resulted in localized inhibition of both in vitro 14C-lipogenesis and in vitro conversion of 14C-testosterone to 5 alpha-reduced radio-metabolites. Topical progesterone did not inhibit in vitro 14C-lipogenesis in the male hamster flank organ. Progesterone added in vitro inhibited 14-C-lipogenesis and 14C-testosterone metabolism in male rat ear sebaceous glands. These results lend support to the hypothesis that inhibition of sebaceous gland lipogenesis by progesterone is a consequence of its inhibitory effect on testosterone metabolism. Such a rationale provides a valid explanation for the clinical findings with progesterone reported by other investigators.
Arch Dermatol Res 1980
PMID:Inhibition of testosterone metabolism and lipogenesis in animal sebaceous glands by progesterone. 723 34

Progesterone, topically applied, prevents the stimulation of the hamster flank organ by testosterone, but not by dihydrotestosterone. 5 alpha-Dihydroprogesterone does not prevent stimulation by either of the two androgenic hormones. Neither progesterone nor 5 alpha-dihydroprogesterone stimulate the flank organ to any extent. Implications on the use of progesterone in acne therapy are discussed.
Br J Dermatol 1980 Apr
PMID:The antiandrogenic effect of progesterone on the hamster flank organ. 738 88

A young girl presented with a purpuric rash on lower limbs, fever, eosinophilia, peripheral neuropathy and progressive renal insufficiency. She developed vesicles, purpuric macules and papules on the head, several nodules on the palmar sides of hands and fingers, splinter haemorrhages, and a disfiguring, facial oedema. A renal biopsy specimen disclosed a focal and segmental necrotizing glomerulonephritis with crescents. Peripheral ANCA with antimyeloperoxidase specificity [P-ANCA (MPO)] was positive and cytoplasmic ANCA with PR3 specificity was negative. Treatment with prednisone and cyclophosphamide was started with a good clinical response, stabilization of renal insufficiency and disappearance of P-ANCA (MPO). Our case fulfils the diagnostic criteria for microscopic polyangiitis (microscopic polyarteritis, MPA), namely a segmental necrotizing and crescentic glomerulonephritis associated with extrarenal vasculitis involving small-sized vessels, without granulomas or asthma. This is a rare disease, which has a poor prognosis in the absence of aggressive therapy, and is infrequently reported in dermatological journals.
Br J Dermatol 1996 Mar
PMID:Microscopic polyangiitis. A systemic vasculitis with a positive P-ANCA. 873 85

This study demonstrates the synthesis and release of prolactin (PRL) from dermal fibroblasts (>98%) in vitro, suggesting a potential local source of PRL in skin. PRL release was first detected in confluent cultures (0.25 x 10(6) plated cells) on or before day 18 and increased to a maximal level of 2 ng/72 h by day 30. Medroxyprogesterone acetate and estradiol (E2) had no effect on PRL release, but prostaglandin E2 (PGE2) reduced the time required for PRL induction to 6-9 days. The steroids and PGE2 together were synergistic, reaching maximal values of approximately 10 ng/72 h after 2 or more weeks of treatment. Dibutyryl-cyclic AMP, a second messenger in prostaglandin signal transduction, was also synergistic with medroxyprogesterone acetate and E2, but induced significant PRL expression in the absence of the steroids (28 and 12 ng/72 h, respectively). The increase in PRL release was not a result of increased cell proliferation, because the PRL-secreting cultures had 32.2 +/- 8.8% less DNA (N = 3 individuals, 93% confidence limit) than control cultures after 3 weeks of treatment with dibutyryl-cyclic AMP, medroxyprogesterone acetate, and E2. Dermal fibroblast PRL was immunologically and electrophoretically identical to decidual and pituitary PR-Ls, and Northern blot analysis demonstrated a PRL mRNA size of 1.15 kb. Maximal PRL release from fibroblast cells was 32.0 +/- 6.1 ng/72 h (mean +/- SD at 95% confidence limit) for a donor population representing both males (n = 15) and females (n = 7) between the ages of 20-week gestation to 52 years. In contrast to term decidual fibroblast cells that also express PRL, dermal fibroblasts did not co-express insulin-like growth factor-binding protein-1.
J Invest Dermatol 1996 Jun
PMID:Human dermal fibroblast cells express prolactin in vitro. 875 65

Autoimmune progesterone dermatitis is a rare manifestation of hypersensitivity to endogenous hormones with polymorphic clinical manifestations. We report a 28-year-old woman with a 5-year history of mucocutaneous erythema multiforme occurring cyclically in the premenstrual period. Progesterone sensitivity was demonstrated by challenge test with medroxyprogesterone acetate. Treatments with oestrogens, tamoxifen and triptorelin had to be withdrawn because of intolerable adverse effects. Oophorectomy finally cured the disease.
Br J Dermatol 1998 Sep
PMID:Autoimmune progesterone dermatitis: treatment with oophorectomy. 976 1


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