Evidence for gonadotrophin secretory and steroidogenic abnormalities in brothers of women with polycystic ovary syndrome

Human Reproduction

Volumn 29, Issue 12, 2014, Pages 2764-2772

  Liu, D M ^a   Torchen, L C ^a   Sung, Y ^b   Paparodis, R ^c   Legro, R S ^d   Grebe, S K ^e   Singh, R J ^e   Taylor, R L ^e   Dunaif, A ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b Ewha Womans University School of Medicine   (South Korea)

^c UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^d PENN STATE COLLEGE OF MEDICINE   (United States)

^e MAYO CLINIC   (United States)

Author keywords

male phenotype; polycystic ovary syndrome; steroidogenesis; steroidogenic enzymes

Indexed keywords

17 HYDROXYPREGNENOLONE; 3(OR 17)BETA HYDROXYSTEROID DEHYDROGENASE; ANDROSTENEDIONE; CORTICOTROPIN; CORTODOXONE; FOLLITROPIN; GLUCOSE; GONADORELIN; GONADOTROPIN; HYDROCORTISONE; HYDROXYPROGESTERONE; LEUPRORELIN; LUTEINIZING HORMONE; PRASTERONE; PRASTERONE SULFATE; STEROID; STEROID 11BETA MONOOXYGENASE; STEROID 17ALPHA MONOOXYGENASE; STEROID 21 MONOOXYGENASE; TESTOSTERONE; TESTOSTERONE 17BETA DEHYDROGENASE;

ADULT; ARTICLE; BODY WEIGHT; CASE CONTROL STUDY; CLINICAL ARTICLE; CLINICAL FEATURE; CONTROLLED STUDY; CORTICOTROPIN TEST; ENZYME ACTIVITY; ETHNICITY; FEMALE; FIRST DEGREE RELATIVE; GENETIC SUSCEPTIBILITY; GLUCOSE BLOOD LEVEL; GONADOTROPIN RELEASE; HEALTH STATUS; HORMONE BLOOD LEVEL; HORMONE DETERMINATION; HUMAN; MALE; OVARY POLYCYSTIC DISEASE; SIBLING; STEROIDOGENESIS; UTERUS; ADOLESCENT; BLOOD; MIDDLE AGED;

17-ALPHA-HYDROXYPREGNENOLONE; 17-ALPHA-HYDROXYPROGESTERONE; ADOLESCENT; ADULT; ANDROSTENEDIONE; CASE-CONTROL STUDIES; CORTODOXONE; DEHYDROEPIANDROSTERONE SULFATE; FEMALE; GONADOTROPINS; HUMANS; MALE; MIDDLE AGED; POLYCYSTIC OVARY SYNDROME; SIBLINGS; STEROIDS;

EID: 84929619596     PISSN: 02681161     EISSN: 14602350     Source Type: Journal    
DOI: 10.1093/humrep/deu282     Document Type: Article

References (50)

1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011; 34(Suppl 1): S62-S69
2. Anderson H, Fogel N, Grebe SK, Singh RJ, Taylor RL, Dunaif A. Infants of women with polycystic ovary syndrome have lower cord blood androstenedione and estradiol levels. J Clin Endocrinol Metab. 2010; 95: 2180-2186
3. Barnes RB, Rosenfield RL, Burstein S, Ehrmann DA. Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome. N Engl J Med. 1989; 320: 559-565
4. Barnes RB, Ehrmann DA, Brigell DF, Rosenfield RL. Ovarian steroidogenic responses to gonadotropin-releasing hormone agonist testing with nafarelin in hirsute women with adrenal responses to adrenocorticotropin suggestive of 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency. J Clin Endocrinol Metab. 1993; 76: 450-455
5. Bruns CM, Baum ST, Colman RJ, Eisner JR, Kemnitz JW, Weindruch R, Abbott DH. Insulin resistance and impaired insulin secretion in prenatally androgenized male rhesus monkeys. J Clin Endocrinol Metab. 2004; 89: 6218-6223
6. Carbunaru G, Prasad P, Scoccia B, Shea P, Hopwood N, Ziai F, Chang YT, Myers SE, Mason JI, Pang S. The hormonal phenotype of Nonclassic 3 betahydroxysteroid dehydrogenase (HSD3). deficiency in hyperandrogenic females is associated with insulin-resistant polycystic ovary syndrome and is not a variant of inherited HSD3B2 deficiency. J Clin Endocrinol Metab. 2004; 89: 783-394
7. Comim FV, Teerds K, Hardy K, Franks S. Increased protein expression of LHCG receptor and 17alpha-hydroxylase/17-20-lyase in human polycystic ovaries. Hum Reprod. 2013; 28: 3086-3092
8. Coviello AD, Sam S, Legro RS, Dunaif A. High prevalence of metabolic syndrome in first-degree male relatives of women with polycystic ovary syndrome is related to high rates of obesity. J Clin Endocrinol Metab. 2009; 94: 4361-4366
9. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndromerevisited: an update on mechanisms and implications. Endocr Rev. 2012; 33: 981-1030
10. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, Zapanti ED, Bartzis MI. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999; 84: 4006-4011
11. Dunaif A, Scott D, Finegood D, Quintana B, Whitcomb R. The insulinsensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1996; 81: 3299-3306
12. Givens JR. Familial polycystic ovarian disease. Endocrinol Metab Clin North Am. 1988; 17: 771-783
13. Goodarzi MO, Jones MR, Antoine HJ, Pall M, Chen YD, Azziz R. Nonreplication of the type 5 17beta-hydroxysteroid dehydrogenase gene association with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008; 93: 300-303
14. Griffing GT, Allen J, Pratt H, Melby JC. Discordance of plasma DHEA-S, DHEA, and cortisol responses with various ACTH regimens. Metabolism. 1985; 34: 631-636
15. Hatch R, Rosenfield RL, Kim MH, Tredway D. Hirsutism: implications, etiology, and management. Am J Obstet Gynecol. 1981; 140: 815-830
16. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab. 1998; 83: 3078-3082
17. Kumar A, Kalra B, Patel AS, Shah S. Development of a sensitive Inhibin B ELISA optimized to eliminate false positive results. Clin Chem. 2013; 59: 107
18. Legro RS, Driscoll D, Strauss JF III, Fox J, Dunaif A. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci USA. 1998; 95: 14956-14960
19. Legro RS, Bentley-Lewis R, Driscoll D, Wang SC, Dunaif A. Insulin resistance in the sisters of women with polycystic ovary syndrome: association with hyperandrogenemia rather than menstrual irregularity. J Clin Endocrinol Metab 2002a; 87: 2128-2133
20. Legro RS, Kunselman AR, Demers L, Wang SC, Bentley-Lewis R, Dunaif A. Elevated dehydroepiandrosterone sulfate levels as the reproductive phenotype in the brothers of women with polycystic ovary syndrome. J Clin Endocr Metab 2002b; 87: 2134-2138
21. Li Y, Liu F, Luo S, Hu H, Li XH, Li SW. Polymorphism T-C of gene CYP17 promoter and polycystic ovary syndrome risk: a meta-Analysis. Gene. 2012; 495: 16-22
22. Marshall JC, Eagleson CA. Neuroendocrine aspects of polycystic ovary syndrome. Endocrinol Metab Clin North Am. 1999; 28: 295-324
23. McCartney CR, Blank SK, Prendergast KA, Chhabra S, Eagleson CA, Helm KD, Yoo R, Chang RJ, Foster CM, Caprio S, et al. Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre-And early pubertal obese girls. J Clin Endocrinol Metab. 2007; 92: 430-436
24. Moghrabi N, Hughes IA, Dunaif A, Andersson S. Deleterious missense mutations and silent polymorphism in the human 17beta-hydroxysteroid dehydrogenase 3 gene (HSD17B3). J Clin Endocrinol Metab. 1998; 83: 2855-2860
25. Moran C, Reyna R, Boots LS, Azziz R. Adrenocortical hyperresponsiveness to corticotropin in polycystic ovary syndrome patients with adrenal androgen excess. Fertil Steril. 2004; 81: 126-131
26. Mortensen M, Rosenfield RL, Littlejohn E. Functional significance of polycystic-size ovaries in healthy adolescents. J Clin Endocrinol Metab. 2006; 91: 3786-3790
27. Mortensen M, Ehrmann DA, Littlejohn E, Rosenfield RL. Asymptomatic volunteers with a polycystic ovary are a functionally distinct but heterogeneous population. J Clin Endocrinol Metab. 2009; 94: 1579-1586
28. Pang SY, Softness B, Sweeney WJ III, New MI. Hirsutism, polycystic ovarian disease, and ovarian 17-ketosteroid reductase deficiency. N Engl J Med. 1987; 316: 1295-1301
29. Pierik FH, Vreeburg JT, Stijnen T, De Jong FH, Weber RF. Serum inhibin B as a marker of spermatogenesis. J Clin Endocrinol Metab. 1998; 83: 3110-3114
30. Qin K, Ehrmann DA, Cox N, Refetoff S, Rosenfield RL. Identification of a functional polymorphism of the human type 5 17beta-hydroxysteroid dehydrogenase gene associated with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006; 91: 270-276
31. Rebar R, Judd HL, Yen SS, Rakoff J, Vandenberg G, Naftolin F. Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. J Clin Invest. 1976; 57: 1320-1329
32. Recabarren SE, Lobos A, Figueroa Y, Padmanabhan V, Foster DL, Sir-Petermann T. Prenatal testosterone treatment alters LH and testosterone responsiveness to GnRH agonist in male sheep. Biol Res. 2007; 40: 329-338
33. Recabarren SE, Rojas-Garcia PP, Recabarren MP, Alfaro VH, Smith R, Padmanabhan V, Sir-Petermann T. Prenatal testosterone excess reduces sperm count and motility. Endocrinology 2008a; 149: 6444-6448
34. Recabarren SE, Sir-Petermann T, Rios R, Maliqueo M, Echiburu B, Smith R, Rojas-Garcia P, Recabarren M, Rey RA. Pituitary and testicular function in sons of women with polycystic ovary syndrome from infancy to adulthood. J Clin Endocrinol Metab 2008b; 93: 3318-3324
35. Rojas-Garcia PP, Recabarren MP, Sarabia L, Schon J, Gabler C, Einspanier R, Maliqueo M, Sir-Petermann T, Rey R, Recabarren SE. Prenatal testosterone excess alters Sertoli and germ cell number and testicular FSH receptor expression in rams. Am J Physiol Endocrinol Metab. 2010; 299: E998-E1005
36. Rosenfield RL, Barnes RB, Ehrmann DA. Studies of the nature of 17-hydroxyprogesterone hyperresponsiveness to gonadotropin-releasinghormone agonist challenge in functional ovarian hyperandrogenism. J Clin Endocrinol Metab. 1994; 79: 1686-1692
37. Rosenfield RL, Perovic N, Ehrmann DA, Barnes RB. Acute hormonal responses to the gonadotropin releasing hormone agonist leuprolide: dose-response studies and comparison to nafarelin-A clinical research center study. J Clin Endocrinol Metab. 1996; 81: 3408-3411
38. Sam S, Legro RS, Essah PA, Apridonidze T, Dunaif A. Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome. Proc Natl Acad Sci USA. 2006; 103: 7030-7035
39. Sam S, Coviello AD, Sung YA, Legro RS, Dunaif A. Metabolic phenotype in the brothers of women with polycystic ovary syndrome. Diabetes Care 2008a; 31: 1237-1241
40. Sam S, Sung YA, Legro RS, Dunaif A. Evidence for pancreatic beta-cell dysfunction in brothers of women with polycystic ovary syndrome. Metabolism 2008b; 57: 84-89
41. Shi Y, Zhao H, Shi Y, Cao Y, Yang D, Li Z, Zhang B, Liang X, Li T, Chen J, et al. Genome-wide association study identifies eight newrisk loci for polycystic ovary syndrome. Nat Genet. 2012; 44: 1020-1025
42. Sir-Petermann T, Angel B, Maliqueo M, Carvajal F, Santos JL, Perez-Bravo F. Prevalence of Type II diabetes mellitus and insulin resistance in parents of women with polycystic ovary syndrome. Diabetologia. 2002; 45: 959-964
43. Sir-Petermann T, Cartes A, Maliqueo M, Vantman D, Gutierrez C, Toloza H, Echiburu B, Recabarren SE. Patterns of hormonal response to the GnRH agonist leuprolide in brothers of women with polycystic ovary syndrome: a pilot study. Hum Reprod. 2004; 19: 2742-2747
44. Spratt DI, Finkelstein JS, Butler JP, Badger TM, Crowley WF Jr. Effects of increasing the frequency of low doses of gonadotropin-releasing hormone (GnRH) on gonadotropin secretion in GnRH-deficient men. J Clin Endocrinol Metab. 1987; 64: 1179-1186
45. Tee MK, Miller WL. Phosphorylation of human cytochrome P450c17 by p38alpha selectively increases 17, 20 lyase activity and androgen biosynthesis. J Biol Chem. 2013; 288: 23903-23913
46. Toscano V, Balducci R, Bianchi P, Mangiantini A, Sciarra F. Ovarian 17-ketosteroid reductase deficiency as a possible cause of polycystic ovarian disease. J Clin Endocrinol Metab. 1990; 71: 288-292
47. Urbanek M, Sam S, Legro RS, Dunaif A. Identification of a polycystic ovary syndrome susceptibility variant in fibrillin-3 and association with a metabolic phenotype. J Clin Endocrinol Metab. 2007; 92: 4191-4198
48. Vink JM, Sadrzadeh S, Lambalk CB, Boomsma DI. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab. 2006; 91: 2100-2104
49. Yildiz BO, Yarali H, Oguz H, Bayraktar M. Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003; 88: 2031-2036
50. Zhou R, Bird IM, Dumesic DA, Abbott DH. Adrenal hyperandrogenism is induced by fetal androgen excess in a rhesus monkey model of polycystic ovary syndrome. J Clin Endocrinol Metab. 2005; 90: 6630-6637