Elevated androgens during puberty in female rhesus monkeys lead to increased neuronal drive to the reproductive axis: A possible component of polycystic ovary syndrome

Human Reproduction

Volumn 27, Issue 2, 2012, Pages 531-540

  McGee, W K ^a,b   Bishop, C V ^a   Bahar, A ^b   Pohl, C R ^c   Chang, R J ^d   Marshall, J C ^e   Pau, F K ^a   Stouffer, R L ^a,b   Cameron, J L ^a,b,c  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF VIRGINIA   (United States)

Author keywords

hyperandrogenism; LH; polycystic ovary syndrome; puberty; testosterone

Indexed keywords

GONADORELIN; LUTEINIZING HORMONE; TESTOSTERONE;

ARTICLE; CONTROLLED STUDY; ECHOGRAPHY; FEMALE; GLUCOSE TOLERANCE; INSULIN SENSITIVITY; MENARCHE; MENSTRUAL CYCLE; MORPHOLOGY; NONHUMAN; OVARY; OVARY POLYCYSTIC DISEASE; PULSATILE HORMONE RELEASE; RHESUS MONKEY;

ANIMALIA; MACACA MULATTA;

EID: 84855890276     PISSN: 02681161     EISSN: 14602350     Source Type: Journal    
DOI: 10.1093/humrep/der393     Document Type: Article

References (63)

1. Abbott DH, Dumesic DA, Eisner JR, Colman JR, Kemnitz JW. Insights into the development of polycystic ovary syndrome (PCOS) from studies of prenatally androgenized female rhesus monkeys. Trends Endocrinol Metab 1998;9:62-67.
2. Abbott DH, Barnett DK, Bruns CM, Dumesic DA. Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum Reprod Update 2005;11:357-374.
3. Abbott DH, Barnett DK, Levine JE, Padmanabhan V, Dumesic DA, Jacoris S, Tarantal AF. Endocrine antecedents of polycystic ovary syndrome in fetal and infant prenatally androgenized female rhesus monkeys. Biol Reprod 2008;79:154-163.
4. Apter D, Cacciatore B, Alfthan H, Stenman U. Serum luteinizing hormone concentrations increase 100-fold in females from 7 years to adulthood, as measured by time-resolved immunofluorometric assay. J Clin Endocrinol Metab 1989;68:53-57.
5. Apter D, Butzow T, Laughlin GA, Yen SSC. Accelerated 24-hour luteinizing hormone pulsatile activity in adolescent girls with ovarian hyperandrogenism: relevance to the developmental phase of polycystic ovarian syndrome. J Clin Endocrinol Metab 1994;79:119-125.
6. Asuncion M, Calvo RM, san Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 2000;85:2434-2438.
7. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004;89:2745-2749.
8. Bachelot A, Laborde K, Bresson JL, Plu-Bureau G, Raynaud A, Bertagna X, Mogenet A, Mansour M, Lucas-Jouy V, Gayno J-P et al. Luteinizing hormone pulsatility in patients with major ovarian hyperandrogenism. J Endocrinol Invest 2007;30:636-646.
9. Barnes RB, Rosenfield RL, Ehrmann DA, Cara JF, Cuttler JF, Levitsky LL, Rosenthal IM. Ovarian hyperandrogenism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women. J Clin Endocrinol Metab 1994;79:1328-1333.
10. Bergman RN, Ider ZY, Bowden CR, Cobelli C. Quantitative estimation of insulin sensitivity. Am J Physiol 1979;236:E667-E677.
11. Bishop CV, Sparman ML, Stanley JE, Bahar A, Zelinski MB, Stouffer RL. Evaluation of antral follicle growth in the macaque ovary during the menstrual cycle and controlled ovarian stimulation by high-resolution ultrasonography. Am J Primatol 2009;71:384-392.
12. Blank SK, Helm KD, McCartney CR, Marshall JC. Polycystic ovary syndrome in adolescence. Ann N Y Acad Sci 2008;1135:76-84.
13. Blank SK, McCartney CR, Chhabra S, Helm KD, Eagleson CA, Chang RJ, Marshall JC. Modulation of GnRH pulse generator sensitivity to progesterone inhibition in hyperandrogenic adolescent girls-Implications for regulation of pubertal maturation. J Clin Endocrinol Metab 2009;94:2360-2366.
14. Blankstein J, Rabinovici J, Goldenberg M, Shaley J, Mehta A, Serr DM, Mashiach S. Changing pituitary reactivity to follicle-stimulating hormone and luteinizing hormone-releasing hormone after induced ovulatory cycles and after anovulation in patients with polycystic ovarian disease. J Clin Endocrinol Metab 1987;65:1164-1167.
15. Boston RC, Stefanovski D, Moate PJ, Sumner AE, Watanabe RM, Bergman RN. MINMOD Millennium: A computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther 2003;5:1003-1015.
16. Cameron JL, Nosbisch C. Suppression of pulsatile luteinizing hormone and testosterone secretion during short term food restriction in the adult male rhesus monkey (Macaca mulatta). Endocrinology 1991;128:1532-1540.
17. Chang RJ. The reproductive phenotype in polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab 2007;3:688-695.
18. Chen MJ, Yang WS, Li L, Chen X. The relationship between anti-Mullerian hormone, androgen and insulin resistance on the number of antral follicles in women with polycystic ovary syndrome. Hum Reprod 2008;23:952-957.
19. Clark MK, Dillon JS, Sowers M, Nichols S. Weight, fat mass, and central distribution of fat increase when women use depotmedroxyprogesterone acetate for contraception. Int J Obes (Lond) 2005;29:1252-1258.
20. Dumesic DA, Schramm RD, Peterson E, Paprocki AM, Zhou R, Abbott DH. Impaired developmental competence of oocytes in adult prenatally androgenized female rhesus monkeys undergoing gonadotropin stimulation for in vitro fertilization. J Clin Endocrinol Metab 2002;87:1111-1119.
21. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989;38:1165-1174.
22. Eagleson CA, Bellows AB, Hu K, Gingrich MB, Marshall JC. Obese patients with polycystic ovary syndrome: evidence that metformin does not restore sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by ovarian steroids. J Clin Endocrinol Metab 2003;88:5158-5162.
23. Evans JI, MacLean AW, Ismail AAA, Love D. Concentrations of plasma testosterone in normal men during sleep. Nature 1971;229:261-262.
24. Foecking EM, Szabo M, Schwartz MB, Levine JE. Neuroendocrine consequences of prenatal androgen exposure in the female rat: absence of luteinizing hormone surges, suppression of progesterone receptor gene expression, and acceleration of the gonadotropin-releasing hormone pulse generator. Biol Reprod 2005;72:1475-1483.
25. Goodman RL, Hotchkiss J, Karsch J, Knobil E. Diurnal variations in serum testosterone concentrations in the adult male rhesus monkey. Biol Reprod 1974;11:624-630.
26. Herod SM, Dettmer AM, Novak MA, Meyer JS, Cameron JL. Sensitivity to stress-induced reproductive dysfunction is associated with a selective but not a generalized increase in activity of the adrenal axis. Am J Physiol Endocrinol Metab 2010a; 300:E28-E36.
27. Herod SM, Pohl CR, Cameron JL. Treatment with a CRH-R1 Antagonist Prevents Stress-Induced Suppression of the Central Neural Drive to the Reproductive Axis in Female Macaques. Am J Physiol Endocrinol Metab 2010b; 300:E19-E27.
28. Hoeger KM. Exercise therapy in polycystic ovary syndrome. Semin Reprod Med 2008;26:93-100.
29. Hunnell NA, Rockcastle NJ, McCormick KN, Sinko LK, Sullivan EL, Cameron JL. Physical activity of adult female rhesus monkeys (Macaca mulatta) across the menstrual cycle. Am J Physiol Endocrinol Metab 2007;292:E1520-E1525.
30. Holmes-Walker DJ, Conway GS, Honour JW, Rumsby G, Jacobs HS. Menstrual disturbance and hypersecretion of progesterone in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clin Endocrinol (Oxf) 1995;43:291-296.
31. Ibanez L, Potau N, Virdis R, Zampolli M, Terzi C, Gussinye M, Carrascosa A, Vicens-Calvet E. Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism. J Clin Endocrinol Metab 1993;76:1599-1603.
32. 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.
33. Legro RS. The genetics of obesity. Lessons for polycystic ovary syndrome. Ann N Y Acad Sci 2000;900:193-202.
34. Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999;84:165-169.
35. Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med 2001;111:607-613.
36. Levin JH, Carmina E, Lobo RA. Is the inappropriate gonadotropin secretion of patients with polycystic ovary syndrome similar to that of patients with adult-onset congenital adrenal hyperplasia? Fertil Steril 1991;56:635-640.
37. Marshall JC, Eagleson CA. Neuroendocrine aspects of polycystic ovary syndrome. Endocrinol Metab Clin North Am 1999;28:295-324.
38. McCartney CR, Eagleson CA, Marshall JC. Regulation of gonadotropin secretion: implications for polycystic ovary syndrome. Semin Reprod Med 2002;20:317-326.
39. McCartney CR, Prendergast KA, Chhabra S, Eagleson CA, Yoo R, Chang RJ, Foster CM, Marshall JC. The association of obesity and hyperandrogenemia during the pubertal transition in girls: obesity as a potential factor in the genesis of postpubertal hyperandrogenism. J Clin Endocrinol Metab 2006;91:1714-1722.
40. McCartney CR, Prendergast KA, Blank SK, Helm KD, Chhabra S, Marshall JC. Maturation of luteinizing hormone (gonadotropin-releasing hormone) secretion across puberty: Evidence for altered regulation in obese peripubertal girls. J Clin Endocrinol Metab 2009;94:56-66.
41. Merriam GR, Wachter KW. Algorithms for the study of episodic hormone secretion. Am J Physiol 1982;243:E310-E318.
42. Midgley AR Jr, Jaffe RB. Regulation of human gonadotropins. X. Episodic fluctuation of LH during the menstrual cycle. J Clin Endocrinol Metab 1971;33:962-969.
43. 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.
44. Ovalle F, Azziz R. Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus. Fertil Steril 2002;77:1095-105.
45. Pache TD, Chadha S, Gooren LJG, Hop WCJ, Jaarsma KW, Dommerholt HBR, Fauser BCJM. Ovarian morphology in long-term androgen-treated female to male transsexuals. A human model for the study of polycystic ovarian syndrome? Histopath 1991;19:445-452.
46. Pasquali R, Antenucci D, Casimirri F, Venturoli S, Paradisi R, Fabbri R, Balestra V, Melchionda N, Barbara L. Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss. J Clin Endocrinol Metab 1989;68:173-179.
47. Pastor CL, Griffin-Korf ML, Aloi JA, Evans WS, Marshall JC. Polycystic ovary syndrome: evidence for reduced sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone. J Clin Endocrinol Metab 1998;83:582-590.
48. Patel K, Coffler MS, Dahan MH, Malcom PJ, Deutsch R, Chang RJ. Relationship of GnRH-stimulated LH release to episodic LH secretion and baseline endocrine-metabolic measures in women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2004;60:67-74.
49. Piro C, Fraioli F, Sciarra F, Conti C. Circadian rhythm of plasma testosterone, cortisol and gonadotropins in normal male subjects. J Steroid Biochem 1973;4:321-329.
50. Ramaswamy S, Seminara SB, Pohl CR, DiPietro MJ, Crowley WF Jr, Plant TM. Effect of continuous intravenous administration of human metastin 45-54 on the neuroendocrine activity of the hypothalamic-pituitary-testicular axis in the adult male rhesus monkey (Macaca mulatta). Endocrinology 2007;148:3364-3370.
51. Rebar R, Judd HL, Rakoff J, Vandenberg G, Naftolin F. Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. J Clin Invest 1976;57:1320-1329.
52. Savabieasfahani M, Lee JS, Herkimer C, Sharma TP, Foster DL, Padmanabhan V. Fetal programming: testosterone exposure of the female sheep during midgestation disrupts the dynamics of its adult gonadotropin secretion during the periovulatory period. Biol Reprod 2005;72:221-229.
53. Shah B, Parnell L, Milla S, Kessler M, David R. Endometrial thickness, uterine, and ovarian ultrasonographic features in adolescents with polycystic ovarian syndrome. J Pediatr Adolesc Gynecol 2010;23:146-152.
54. Sharma TP, Herkimer C, West C, Ye W, Birch R, Robinson JE, Foster DL, Padmanabhan V. Fetal programming: prenatal androgen disrupts positive feedback actions of estradiol but does not affect timing of puberty in female sheep. Biol Reprod 2002;66:924-933.
55. Silfen ME, Denburg MR, Manibo AM, Lobo RA, Jaffe R, Ferin M, Levine LS, Oberfield SE. Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese and obese adolescents. J Clin Endocrinol Metab 2003;88:4682-4688.
56. Steil GM, Volund A, Kahn SE, Bergman RN. Reduced sample number for calculation of insulin sensitivity and glucose effectiveness from the minimal model. Suitability for use in population studies. Diabetes 1993;42:250-256.
57. Terasawa E, Bridson WE, Nass TE, Noonan JJ, Dierschke DJ. Developmental changes in the luteinizing hormone secretory pattern in peripubertal female rhesus monkeys: comparisons between gonadally intact and ovariectomized animals. Endocrinology 1984;115:2233-2240.
58. Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA. Androgens stimulate early stages of follicular growth in the primate ovary. J Clin Invest 1998;101:2622-2629.
59. Waldstreicher J, Santoro NF, Hall JE, Filicori M, Crowley WF Jr Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: indirect evidence for partial gonadotroph desensitization. J Clin Endocrinol Metab 1988;66:165-172.
60. Williams NI, Caston-Balderrama AL, Helmreich DL, Parfitt DB, Nosbisch C, Cameron JL. Longitudinal changes in reproductive hormones and menstrual cyclicity in cynomolgus monkeys during strenuous exercise training: abrupt transition to exercise-induced amenorrhea. Endocrinology 2001;142:2381-2389.
61. Yen SS, Tsai CC, Naftolin F, Vandenberg G, Ajabor L. Pulsatile patterns of gonadotropin release in subjects with and without ovarian function. J Clin Endocrinol Metab 1972;34:671-675.
62. Yen SS, Lasley BL, Wang CF, Leblanc H, Siler TM. The operating characteristics of the hypothalamic-pituitary system during the menstrual cycle and observations of biological action of somatostatin. Recent Prog Horm Res 1975;31:321-363.
63. Zumoff B, Freeman R, Coupey S, Saenger P, Markowitz M, Kream J. A chronobiologic abnormality in luteinizing hormone secretion in teenage girls with the polycystic-ovary syndrome. N Engl J Med 1983;309:1206-1209.