Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002453 (amenorrhea)
 6,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-eight women with amenorrhea, galactorrhea and hyperprolactinemia without hirsutism were studied before and after bromocriptine therapy for 2 months. Compared to 15 euprolactinemic controls, hyperprolactinemic women had elevated levels of dehydroepiandrosterone sulfate and androstenedione and lower levels of total testosterone (T), and androst-5-ene-3 beta, 17 beta-diol (Adiol), and 17 beta-estradiol (P less than 0.05). Unbound T and unbound Adiol were significantly elevated, while sex hormone-binding globulin binding capacity was decreased (P less than 0.05) and corticosteroid-binding globulin binding capacity was normal. After treatment with bromocriptine, dehydroepiandrosterone sulfate and androstenedione decreased to control levels, as did unbound Adiol, while 17 beta-estradiol and sex hormone-binding globulin binding capacity levels increased significantly (P less than 0.05). Five hyperprolactinemic women underwent ACTH stimulation tests before and after treatment, and the results were compared to those of seven controls. Steroid ratios in response to ACTH suggested normal 3 beta ol-dehydrogenase-isomerase, 17-20-desmolase and 17 beta-hydroxysteroid dehydrogenase enzymatic activities in hyperprolactinemia. Basal steroid ratios of T to 5 alpha-androstane-17 beta-01-3-one) (DHT) and of unbound T to unbound dihydrotestosterone were elevated (P less than 0.05), suggesting reduced 5 alpha-reductase activity in hyperprolactinemia which is normalized after treatment. Hirsutism was not present in these patients with hyperprolactinemia despite elevated levels of unbound T and Adiol, and may be explained by reduced 5 alpha-reductase activity. Our data suggest that the increased levels of androgens in these patients result from the hyperprolactinemia.
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PMID:Normalization of androgen and sex hormone-binding globulin levels after treatment of hyperprolactinemia. 629 89

Polycystic ovary syndrome (PCOS) is a common heterogenous endocrine disorder associated with amenorrhoea (or oligomenorrhoea), hyperandrogenism, hirsutism, obesity, insulin resistance, and an approximately 7-fold increased risk of type 2 diabetes mellitus (NIDDM - non-insulin dependent diabetes mellitus). It is a leading cause of female infertility. The prevalence of PCOS among reproductive-age women has been estimated at 4%-12%. Familial aggregation of this syndrome is well established. There are also ethnic and racial variations in the prevalence of the syndrome and its symptoms. Multiple biochemical pathways have been implicated in the pathogenesis of PCOS. Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism (StAR, CYP11, CYP17, CYP19 HSD17B1-3, HSD3B1-2), gonadotropin and gonadal hormones action (ACTR1, ACTR2A-B, FS, INHA, INHBA-B, INHC, SHBG, LHCGR, FSHR, MADH4, AR), obesity and energy regulation (MC4R, OB, OBR, POMC, UCP2-3), insulin secretion and action (IGF1, IGF1R, IGFBPI1-3, INS VNTR, IR, INSL, IRS1-2, PPARG) and many others. Most women with PCOS, both obese and lean, have a degree of insulin resistance. The minisatellite of insulin gene (INS VNTR), especially class III alleles and III/III genotypes might not only determine the predisposition to anovulatory PCOS but also the concomitant risk for development of type 2 diabetes. The function of the insulin receptor (IR) is probably normal in woman with PCOS. However abnormal serine phosphorylation in the receptor may impair signal transduction accounting for a post-binding defect in insulin action. Serine phosphorylation is also involved in the postranslational regulation of 17,20-lyase activity (CYP17). There may be a common aetiology for both insulin resistance and hyperandrogenism. Polymorphic alleles of both IRS-1 and IRS-2 (insulin receptor substrate 1 - 2), alone or in combination, may have a functional impact on the insulin-resistant component of PCOS. There is no evidence to suggest that follistatin gene polymorphisms play a role in the pathogenesis of insulin resistance in PCOS women. PCOS appears to be associated with the absence of the four-repeat-units allele in a polymorphic region of pentanucleotide (TTTTA)n repeats within CYP11A gene, which encodes cytochrome P450scc. It has been hypothesized that up-regulation of this enzyme could lead to increased androgen production. There is no evidence of any association of alleles of CYP19 gene (encoding cytochrome P450arom) with PCOS. Association exists between androgen receptor gene (AR) polymorphisms an androgens action in PCOS. Increased hirustism and decreased CAG repeat length within AR gene has been also demonstrated in women with normal testosterone levels. Expression of estrogen receptor (ERs) as well as 5-alpha-reeducates (SRD5A1-2 genes) activity was analysed in granulosa (GC) and theca cells (TC). The results of this study demonstrate that there are significant alterations in the expression of ERalpha and ERbeta in PCOS that may be related to abnormal follicular development. On the other hand elevated SRD5A activity in polycystic ovaries supported the hypothesis that 5-alpha-reduced androgens may play a role in the pathogenesis of the syndrome. The genetic aetiology of PCOS remains unknown. There are a number of interlinking factors that affects expression of PCOS. Single cause of PCOS is unlikely. Other possible mechanisms in pathogenesis of PCOS are discussed.
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PMID:[Genetic aspects of polycystic ovary syndrome]. 1635 Jul 21