Insulin as an Effector of Human Ovarian and Adrenal Steroid Metabolism

Abraham, 1974, Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle, J Clin Endocrinol Metab, 39, 340, 10.1210/jcem-39-2-340 Adashi, 1982, Insulin augmentation of testosterone production in a primary culture of rat testicular cells, Biol Reprod, 26, 270, 10.1095/biolreprod26.2.270 Barbieri, 1983, Hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome: A common endocrinopathy with distinct pathophysiologic features, Am J Obstet Gynecol, 147, 90, 10.1016/0002-9378(83)90091-1 Barbieri, 1986, Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism, J Clin Endocrinol Metab, 62, 904, 10.1210/jcem-62-5-904 Barbieri, 1988, The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism, Fertil Steril, 50, 197, 10.1016/S0015-0282(16)60060-2 Barbieri, 1988, Hyperinsulinemia and ovarian hyperandrogenism. Cause and effect, Endocrinol Metab Clin North Am, 17, 685, 10.1016/S0889-8529(18)30405-5 Barnes, 1989, Pituitary-ovarian responses to nafarelin in the polycystic ovary syndrome, N Engl J Med, 320, 559, 10.1056/NEJM198903023200904 Bates, 1982, Effect of body weight reduction on plasma androgens in obese, infertile women, Fertil Steril, 38, 406, 10.1016/S0015-0282(16)46571-4 Baxter, 1987, Diurnal rhythm of growth hormone—independent binding protein for insulin-like growth factors in human plasma, J Clin Endocrinol Metab, 62, 432, 10.1210/jcem-65-3-432 Blanco, 1981, The effect of insulin and luteinizing hormone treatment on serum concentrations of testosterone and dihydrotestosterone and testicular 3β-hydroxysteroid dehydrogenase activity in intact and hypophysectomized diabetic rats, Endocrinology, 109, 1248, 10.1210/endo-109-4-1248 Blay, 1989, The nature and function of polypeptide growth factor receptors in the human placenta, J Dev Physiol, 12, 237 Burghen, 1980, Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease, J Clin Endocrinol Metab, 50, 113, 10.1210/jcem-50-1-113 Cara, 1988, Insulin-like growth factor I and insulin potentiate luteinizing hormone-induced androgen synthesis by rat ovarian thecal-interstitial cells, Endocrinology, 123, 733, 10.1210/endo-123-2-733 Cara, 1990, Insulin-like growth factor-I enhances luteinizing hormone binding to rat ovarian theca-interstitial cells, J Clin Invest, 86, 560, 10.1172/JCI114745 Chang, 1983, Insulin resistance in nonobese patients with polycystic ovarian disease, J Clin Endocrinol Metab, 57, 356, 10.1210/jcem-57-2-356 Conover, 1990, Insulin regulation of insulin-like growth factor-binding protein production in cultured HepG2 cells, J Clin Endocrinol Metab, 70, 1062, 10.1210/jcem-70-4-1062 Diamond, 1991, Effect of acute physiological elevations of insulin on circulating androgen levels in nonobese women, J Clin Endocrinol Metab, 72, 883, 10.1210/jcem-72-4-883 Dunaif, 1988, The impact of obesity and chronic hyperinsulinemia on gonadotropin release and gonadal steroid secretion in the polycystic ovary syndrome, J Clin Endocrinol Metab, 66, 131, 10.1210/jcem-66-1-131 Dunaif, 1989, Insulin administration alters gonadal steroid metabolism independent of changes in gonadotropin secretion in insulin resistant women with the polycystic ovary syndrome, J Clin Invest, 83, 23, 10.1172/JCI113864 Dunaif, 1989, Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome, Diabetes, 38, 1165, 10.2337/diab.38.9.1165 Dunaif, 1990, Suppression of hyperandrogenism does not improve peripheral or hepatic insulin resistance in the polycystic ovary syndrome, J Clin Endocrinol Metab, 70, 699, 10.1210/jcem-70-3-699 Erickson, 1990, The effects of insulin and insulin-like growth factors-I and -II on estradiol production by granulosa cells of polycystic ovaries, J Clin Endocrinol Metab, 70, 894, 10.1210/jcem-70-4-894 Falcone, 1990, Androgen response to endogenous insulin secretion during the frequently sampled intravenous glucose tolerance test in normal and hyperandrogenic women, J Clin Endocrinol Metab, 71, 1653, 10.1210/jcem-71-6-1653 Farah, 1990, Bimodal correlation between the circulating insulin level and the production rate of dehydroepiandrosterone: Positive correlation in controls and negative correlation in the polycystic ovary syndrome with acanthosis nigricans, J Clin Endocrinol Metab, 70, 1075, 10.1210/jcem-70-4-1075 Flier, 1985, Acanthosis nigricans in obese women with hyperandrogenism. Characterization of an insulin-resistant state distinct from the Type A and B syndromes, Diabetes, 34, 101, 10.2337/diab.34.2.101 Garzo, 1984, Aromatase activity in human granulosa cells during follicular development and the modulation of follicle-stimulating hormone and insulin, Am J Obstet Gynecol, 148, 657, 10.1016/0002-9378(84)90769-5 Gates, 1987, Characterization of insulin-like growth factor I binding to human granulosa cells obtained during in vitro fertilization, J Recept Res, 7, 885, 10.3109/10799898709054568 Geffner, 1986, Persistence of insulin resistance in polycystic ovarian disease after inhibition of ovarian steroid secretion, Fertil Steril, 45, 327, 10.1016/S0015-0282(16)49211-3 Givens, 1988, Familial polycystic ovarian disease, Endocrinol Metab Clin North Am, 17, 771, 10.1016/S0889-8529(18)30409-2 Grunberger, 1988, Insulin receptors in normal and disease states, Clin Endocrinol Metab, 12, 191, 10.1016/S0300-595X(83)80036-X Gulati, 1989, The effect of the insulin mediator on the metabolism of androst-4-ene-3,17-dione in isolated rat hepatocytes, Biochem Pharmacol, 38, 4415, 10.1016/0006-2952(89)90650-3 Haffner, 1988, The relationship of sex hormones to hyperinsulinemia and hyperglycemia, Metabolism, 37, 683, 10.1016/0026-0495(88)90091-1 Harlass, 1984, Weight loss is associated with correction of gonadotropin and sex steroid abnormalities in the obese anovulatory female, Fertil Steril, 42, 649, 10.1016/S0015-0282(16)48154-9 Hernandez, 1988, Somatomedin-C/insulin-like growth factor I as an enhancer of androgen biosynthesis by cultured rat ovarian cells, Endocrinology, 122, 1603, 10.1210/endo-122-4-1603 Hubert GD, Schriock ED, Givens JR, et al: Insulin suppression of adrenal androgen concentrations during glucose tolerance testing in normal women [abstract 31]. In Scientific Program and Abstracts for the 37th Annual Meeting of the Society for Gynecologic Investigation, 1990, p 112 Hussin, 1987, The effect of insulin on steroid metabolism in isolated rat hepatocytes, Biochem Pharmacol, 36, 3155, 10.1016/0006-2952(87)90626-5 Imperato-McGinley, 1978, Primary amenorrhea associated with hirsutism, acanthosis nigricans, dermoid cysts of the ovaries and a new type of insulin resistance, Am J Med, 65, 389, 10.1016/0002-9343(78)90838-0 Jarrett, 1985, Insulin binding to human ovaries, J Clin Endocrinol Metab, 60, 460, 10.1210/jcem-60-3-460 Kahn, 1976, The syndrome of insulin resistance and acanthosis nigricans, N Engl J Med, 294, 739, 10.1056/NEJM197604012941401 Kiddy, 1990, Differences in clinical and endocrine features between obese and non-obese subjects with polycystic ovary syndrome: An analysis of 263 consecutive cases, Clin Endocrinol (Oxf), 32, 213, 10.1111/j.1365-2265.1990.tb00857.x Koistinen, 1990, Human granulosa cells contain insulin-like growth factor-binding protein (IGF BP-1) mRNA, Clin Endocrinol (Oxf), 32, 635, 10.1111/j.1365-2265.1990.tb00907.x Kramer, 1990, Differential modulation of ACTH-stimulated cortisol and androstenedione secretion by insulin, J Steroid Biochem, 36, 33, 10.1016/0022-4731(90)90111-5 Liu, 1990, Marked attenuation of ultradian and circadian rhythms of dehydroepiandrosterone in postmenopausal women: Evidence for a reduced 17,20-desmolase enzymatic activity, J Clin Endocrinol Metab, 71, 900, 10.1210/jcem-71-4-900 McClanahan, 1990, Insulin inhibits adrenal 17,20-lyase activity, Clin Res, 38, 979A Micic, 1988, Androgen levels during sequential insulin euglycemic clamp studies in patients with polycystic ovary disease, J Steroid Biochem, 31, 995, 10.1016/0022-4731(88)90344-5 Migeon, 1957, Dehydroepiandrosterone and androsterone levels in human plasma. Effect of age and sex; day-to-day and diurnal variations, J Clin Endocrinol Metab, 17, 1051, 10.1210/jcem-17-9-1051 Möller, 1988, Detection of an alteration in the insulin-receptor gene in a patient with insulin resistance, acanthosis nigricans, and the polycystic ovary syndrome (Type A insulin resistance), N Engl J Med, 319, 1526, 10.1056/NEJM198812083192306 Morley, 1989, Insulin enhances luteinizing hormone-stimulated steroidogenesis by porcine theca cells, Biol Reprod, 40, 735, 10.1095/biolreprod40.4.735 Nagamani, 1986, Hyperinsulinemia in hyperthecosis of the ovaries, Am J Obstet Gynecol, 154, 384, 10.1016/0002-9378(86)90676-9 Nestler, 1987, Modulation of aromatase and P450 cholesterol side-chain cleavage enzyme activities of human placental cytotrophoblasts by insulin and insulin-like growth factor I, Endocrinology, 121, 1845, 10.1210/endo-121-5-1845 Nestler, 1987, The effects of hyperinsulinemia on serum testosterone, progesterone, dehydroepiandrosterone sulfate, and cortisol levels in normal women and in a woman with hyperandrogenism, insulin resistance, and acanthosis nigricans, J Clin Endocrinol Metab, 64, 180, 10.1210/jcem-64-1-180 Nestler, 1989, Insulin and insulin-like growth factor I stimulate the 3β-hydroxysteroid dehydrogenase activity of human placental cytotrophoblasts, Endocrinology, 125, 2127, 10.1210/endo-125-4-2127 Nestler, 1989, The central role of obesity (hyperinsulinemia) in the pathogenesis of the polycystic ovary syndrome, Am J Obstet Gynecol, 161, 1095, 10.1016/0002-9378(89)90640-6 Nestler, 1989, Suppression of serum insulin by diazoxide reduces serum testosterone levels in obese women with polycystic ovary syndrome, J Clin Endocrinol Metab, 68, 1027, 10.1210/jcem-68-6-1027 Nestler, 1989, Suppression of serum dehydroepiandroster one sulfate levels by insulin: An evaluation of possible mechanisms, J Clin Endocrinol Metab, 69, 1040, 10.1210/jcem-69-5-1040 Nestler, 1990, Increased transcapillary escape rate of albumin in nondiabetic men in response to hyperinsulinemia, Diabetes, 39, 1212, 10.2337/diab.39.10.1212 Nestler, 1990, Suppression of serum insulin by diazoxide does not alter serum testosterone or sex hormone-binding globulin levels in healthy nonobese women, Am J Obstet Gynecol, 163, 1243, 10.1016/0002-9378(90)90698-7 Nestler, 1991, A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome, J Clin Endocrinol Metab, 72, 83, 10.1210/jcem-72-1-83 Nestler JE, Romero G, Huang LC, Zhang C, Larner J: Insulin mediators are the signal transduction system responsible for insulin’s actions on human placental steroidogenesis. Endocrinology 129: in press (December 1991) Nissley, 1984, Somatomedin/insulin-like growth factor tissue receptors, Clin Endocrinol Metab, 13, 43, 10.1016/S0300-595X(84)80008-0 Orentreich, 1984, Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood, J Clin Endocrinol Metab, 59, 551, 10.1210/jcem-59-3-551 Pardridge, 1986, Serum bioavailability of sex steroid hormones, Clin Endocrinol Metab, 15, 259, 10.1016/S0300-595X(86)80024-X Parker, 1989, Control of adrenal androgen secretion, 355 Pasquali, 1983, Insulin resistance in patients with polycystic ovaries: Its relationship to body weight and androgen levels, Acta Endocrinol (Copenh), 104, 110, 10.1530/acta.0.1040110 Pasquali, 1986, Effect of weight loss and antiandrogenic therapy on sex hormone blood levels and insulin resistance in obese patients with polycystic ovaries, Am J Obstet Gynecol, 154, 139, 10.1016/0002-9378(86)90410-2 Peiris, 1989, The relationship of insulin to sex hormone binding globulin: Role of adiposity, Fertil Steril, 52, 69, 10.1016/S0015-0282(16)60791-4 Pekonen, 1989, Decreased 34K insulin-like growth factor binding protein in polycystic ovarian disease, Fertil Steril, 51, 972, 10.1016/S0015-0282(16)60728-8 Plymate, 1981, Obesity and its role in polycystic ovary syndrome, J Clin Endocrinol Metab, 52, 1246, 10.1210/jcem-52-6-1246 Plymate, 1988, Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin, J Clin Endocrinol Metab, 67, 460, 10.1210/jcem-67-3-460 Poretsky, 1984, Specific insulin binding sites in human ovary, J Clin Endocrinol Metab, 59, 809, 10.1210/jcem-59-4-809 Poretsky, 1987, The gonadotropic function of insulin, Endocr Rev, 8, 132, 10.1210/edrv-8-2-132 Poretsky, 1985, Distribution and characterization of insulin and insulin-like growth factor I receptors in normal human ovary, J Clin Endocrinol Metab, 61, 728, 10.1210/jcem-61-4-728 Poretsky, 1990, Type I insulin-like growth factor receptors in human ovarian stroma, Horm Res, 33, 22, 10.1159/000181441 Poretsky, 1990, Regulation of human ovarian insulin receptors in vivo, Metabolism, 39, 161, 10.1016/0026-0495(90)90070-S Reed, 1989, Regulation of steroid synthesis and metabolism by growth factors, Clin Endocrinol (Oxf), 31, 511, 10.1111/j.1365-2265.1989.tb01275.x Richards, 1985, Obesity, acanthosis nigricans, insulin resistance, and hyperandrogenemia: Pediatric perspective and natural history, I Pediatr, 107, 893, 10.1016/S0022-3476(85)80182-7 Rosenfield, 1990, Dysregulation of cyctochrome P450cl7a as the cause of polycystic ovary syndrome, Fertil Steril, 53, 785, 10.1016/S0015-0282(16)53510-9 Rowe, 1981, Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man, Diabetes, 30, 219, 10.2337/diab.30.3.219 von Schoultz, 1989, On the regulation of sex-hormone-binding globulin—a challenge of an old dogma and outlines of an alternative mechanism, J Steroid Biochem, 32, 327, 10.1016/0022-4731(89)90272-0 Seppälä, 1984, Human preovulatory follicular fluid, luteinized cells of hyperstimulated preovulatory follicles, and corpus luteum contain placental protein 12, J Clin Endocrinol Metab, 58, 505, 10.1210/jcem-58-3-505 Shoupe, 1983, Insulin resistance in polycystic ovary syndrome, Am J Obstet Gynecol, 147, 588, 10.1016/0002-9378(83)90023-6 Shoupe, 1984, The influence of androgens on insulin resistance, Fertil Steril, 41, 385, 10.1016/S0015-0282(16)47716-2 Smith, 1987, Androgen and insulin response to an oral glucose challenge in hyperandrogenic women, Fertil Steril, 48, 72, 10.1016/S0015-0282(16)59293-0 Stuart, 1986, Insulin resistance with acanthosis nigricans: The roles of obesity and androgen excess, Metabolism, 35, 197, 10.1016/0026-0495(86)90201-5 Stuart, 1987, Hyperinsulinemia and hyperandrogenemia: in vivo response to insulin infusion, Obstet Gynecol, 69, 921 Suikkari, 1988, Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein, J Clin Endocrinol Metab, 66, 266, 10.1210/jcem-66-2-266 Suikkari, 1989, Low levels of low molecular weight insulin-like growth factor-binding protein in patients with polycystic ovarian disease, Hum Reprod, 4, 136, 10.1093/oxfordjournals.humrep.a136858 Taylor, 1982, Insulin resistance associated with androgen excess in women with autoantibodies to the insulin receptor, Ann Intern Med, 97, 851, 10.7326/0003-4819-97-6-851 Veldhuis, 1983, Mechanisms subserving the trophic actions of insulin on ovarian cells, J Clin Invest, 72, 1046, 10.1172/JCI111029 Veldhuis, 1986, Insulin regulates low-density lipoprotein binding and degradation by swine granulosa cells, Endocrinology, 118, 2242, 10.1210/endo-118-6-2242 Veldhuis, 1986, The insulin-like growth factor, somatomedin C, induces the synthesis of cholesterol side-chain cleavage cytochrome P-450 and adrenodoxin in ovarian cells, J Biol Chem, 261, 2499, 10.1016/S0021-9258(17)35812-X Yen, 1980, The polycystic ovary syndrome, Clin Endocrinol (Oxf), 12, 177, 10.1111/j.1365-2265.1980.tb02132.x Yoshimasa, 1988, Insulin-resistant diabetes due to a point mutation that prevents insulin proreceptor processing, Science, 240, 784, 10.1126/science.3283938