SINDROME DE OVARIO POLIQUISTICO COMO MODELO CLINICO DE EXPOSICION PRENATAL A ANDROGENOS

SINDROME DE OVARIO POLIQUISTICO COMO MODELO CLINICO DE EXPOSICION PRENATAL A ANDROGENOS

(especial para SIIC © Derechos reservados)
Recientemente, hemos podido establecer que las embarazadas con síndrome de ovario poliquístico presentan niveles androgénicos significativamente más altos que las embarazadas normales, lo que abre la posibilidad que los hijos de estas mujeres pudiesen haber estado sometidos a un ambiente esteroidal anormal durante su vida fetal.
sir9.jpg Autor:
Sir Petermann, Teresa
Columnista Experto de SIIC

Institución:
Laboratorio de Endocrinología y Metabolismo Facultad de Medicina Occidente Universidad de Chile Santiago, Chile


Artículos publicados por Sir Petermann, Teresa
Coautores
Manuel Alejandro Maliqueo Yevilao*  Pedro Pablo Rojas García**  Sergio Edmundo Recabarren Morgado*** 
Profesor Asistente. Facultad de Medicina. Universidad de Chile*
Profesor Asistente. Facultad de Medicina Veterinaria, Universidad de Concepción**
Profesor Titular. Facultad de Medicina Veterinaria, Universidad de Concepción***
Recepción del artículo
30 de Agosto, 2004
Aprobación
30 de Septiembre, 2004
Primera edición
28 de Febrero, 2005
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
Se ha propuesto que la exposición prenatal a andrógenos (EPA) durante la vida fetal en forma experimental, accidental o patológica podría producir una serie de cambios del eje reproductivo y de la homeostasis glucídica del feto femenino que se harían evidentes en su vida posnatal y semejarían aquellos descritos en el síndrome de ovario poliquístico (SOP). Si bien la EPA podría estar involucrada en el desarrollo del SOP no se ha establecido si la madre con SOP podría constituir una fuente de exceso de andrógenos para el feto. En la hiperplasia virilizante congénita, un modelo clásico de EPA, podría ser la corteza suprarrenal hiperandrogénica del propio feto el origen del exceso prenatal de andrógenos, mientras que en el SOP este origen parece más incierto. Recientemente, hemos podido establecer que las embarazadas con SOP presentan niveles androgénicos significativamente más altos que las embarazadas normales, lo que abre la posibilidad que los hijos de estas mujeres pudiesen haber estado sometidos a un ambiente esteroidal anormal durante su vida fetal, el cual podría afectar tanto al feto femenino como masculino. Futuros estudios permitirán evaluar el efecto a largo plazo de este exceso de andrógenos prenatales sobre la descendencia de madres con SOP con el fin de establecer si el SOP debería ser tratado durante el embarazo con el fin de evitar el exceso de andrógenos.

Palabras clave
Síndrome de ovario poliquístico, exposición prenatal a andrógenos, androgenización fetal


Artículo completo

(castellano)
Extensión:  +/-6.09 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

Abstract
It has been proposed that androgen excess during fetal life either experimentally, accidentally or pathologically will produce changes in the reproductive axis and glucose homeostasis of the adult female which resemble those observed in the polycystic ovary syndrome (PCOS). Although androgen excess during pregnancy has been proposed to be involved in the development of PCOS, it has not been established if PCOS mothers could provide a potential source of androgen excess for the fetus. In women with a classical 21-hydroxylase deficiency, the fetal suprarrenal cortex of the fetus will be the source of the androgen excess. In the case of the PCOS, this origin is uncertain. We have recently demonstrated a significant increase in serum androgen concentrations during pregnancy in PCOS women compared to normal pregnant women, which opens the possibility that children of PCOS women could be exposed to an abnormal steroid milieu during fetal life affecting either the female or male fetus. Further studies are needed to evaluate the potential long effect of this prenatal androgen excess on baby girls and boys born to PCOS mother in order to establish if PCOS women should be treated during pregnancy in order to avoid the androgen excess.

Key words
Polycystic ovary syndrome, prenatal androgen excess, fetal androgen excess


Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Farmacología, Obstetricia y Ginecología
Relacionadas: Bioquímica, Diagnóstico por Laboratorio, Endocrinología y Metabolismo, Medicina Interna



Comprar este artículo
Extensión: 6.09 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra



Enviar correspondencia a:
Sir Petermann, Teresa
Patrocinio y reconocimiento:
Agradecimientos: Esta línea de investigación está financiada por el Fondo de Desarrollo Científico y Tecnológico de Chile (FONDECYT) mediante los proyectos 1030487, 1020232 y 1970291.
Bibliografía del artículo
  1. Ehrmann DA, Barnes RB, Rosenfield EL y col. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999; 22:141-146.
  2. Legro RS, Kunselman A, Dodson W y col. Prevalence and predictors risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected wome. J. Clin. Endocrinol. Metab. 1999; 84:165-169.
  3. Ibáñez L, Potau N, Francois I y col. Precocious pubarche, hyperinsulinism and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J. Clin. Endocrinol. Metab. 1998; 83:3558-3562.
  4. Ibáñez L, Potau N, Chacon P y col. Hyperinsulinemia, dyslipidemia and cardiovascular risk in girls with a history of premature pubarche. Diabetologia 1998; 41:1057-1063.
  5. Ibáñez L, DiMartino-Nardi J, Potau N y col. Premature adrenarche-normal variant forerunner of adult disease. Endrocr Rev 2000; 21:671-696.
  6. Van Hooff MHA, Voorhozst FJ, Kaptein MBM y col. Endocrine features of polycystic ovary syndrome in a random population sample of 14-16 year old adolescents. Hum Reprod 1999; 14:2223-2229.
  7. Rosenfield RL, Ghai K, Erhmann DA y col. Diagnosis of the polycystic ovary syndrome in adolescence: comparision of adolescent and adult hyperandrogenism. J. Pediatr. Endocrinol. Metab. 2000; 13(Supp 5):1285-1289.
  8. Apter D, Bützow T, Laughlin GA y col. Metabolic features of polycystic ovary syndrome are found in adolescent girls with hyperandrogenism. J. Clin. Endocrinol. Metab. 1995; 80:2966-2973.
  9. Zawdaki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rationale approach. En: Polycystic ovary syndrome, ed. por Dunaif A, Givens JR, Haseltine F, Merriam GR. Boston: Blackwell 1992; 377-384.
  10. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19:41-47.
  11. Bergh C, Carlsson B, Olsson JH. Regulation of androgen production in cultured human thecal cells by insulin-like growth factor I and insulin. Fertil. Steril. 1993; 59:323-331.
  12. Ehrmann DA, Barnes RB, Rosenfield EL. Polycystic ovary syndrome as a form functional ovarian hyperandrogenism due to dysregulation of androgen secretion. Endocr. Rev. 1995; 16:322-353.
  13. Gharani N, Waterworth DM, Batty S y col. Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism. Hum. Mol. Genet. 1997; 6:397-402.
  14. Moran C, Azziz R. The role of suprarrenal cortex in polycystic ovary syndrome. Obstet. Gynecol. Clin. North. Am. 2001; 28:63-75.
  15. Barnes R, Rosenfield R, Burstein S y col. Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome. N. Engl. J . Med. 1989; 320:559-565.
  16. Rosenfield RL, Barnes RB, Cara JF y col. Dysregulation of cytochrome P45017 as the cause of polycystic ovarian syndrome. Fertil. Steril. 1990; 53:785-791.
  17. Fruzzetti F, De Lorenzo D, Ricci C y col. Ovarian influences on suprarrenal androgen secretion in polycystic ovary syndrome. Fertil. Steril. 1995; 63:734-741.
  18. Gonzalez F, Hatala DA, Speroff L. Suprarrenal and ovarian steroid hormone responses to gonadotropin-releasing hormone agonist treatment in polycystic ovary syndrome. Am. J. Obstet. Gynecol. 1991; 165:535-545.
  19. Adashi E, Hsueh A, Yen S. Insulin enhacement of luteinizing hormone and follicle-stimulating hormone release by cultured pituitary cells. Endocrinology 1981; 108:1441-1449.
  20. Yen SSC, Vela P, Rankin J. Inappropiate secretion of follicle stimulating hormone and luteinizing hormone in Polycystic Ovarian Disease. J. Clin. Endocrinol. Metab. 1970; 30:435-442.
  21. Rebar R, Judd HL, Yen SSC y col. Characterization of the inappropriate gonadotrophin secretion in polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 1976; 57:1320-1329.
  22. Sir Petermann T. 1997 ¿Modulan los andrógenos la secreción de hormona luteinizante en mujeres hiperandrogénicas. Rev. Med. Chile. 1997; 125:710-718.
  23. Sir Petermann T, Piwonka V, Perez F y col. Are circulating leptin and luteinizing hormone synchronized in patients with polycystic ovary syndrome. Hum Reprod. 1999; 14:1435-1439.
  24. Sir Petermann T, Recabarren SE, Lobos A y col. Secretory pattern of leptin and LH during lactational amenorrhoea in breastfeeding normal and polycystic ovarian syndrome women. Hum Reprod. 2001; 16:244-249.
  25. Sir Petermann T, Devoto L, Maliqueo M y col. Resumption of ovarian function during lactational amenorrhoea in breastfeeding women with polycystic ovary syndrome: endocrine aspects. Hum Reprod. 2001; 16:1603-1610.
  26. Abbott DH, Dumesic DA, Eisner JR y col. Insights into the development of polycystic ovary syndrome (PCOS) from studies of prenatally androgenized female Rhesus monkeys. Trends Endocrinology and Metabolism. 1998; 9:62-67.
  27. Zumoff B, Freeman R, Coupey S. A chronobiologic abnormality in luteinizing hormone secretion in teenage girls with the polycystic ovary síndrome. N. Engl. J. Med. 1983; 309:1206-1209.
  28. Apter D, Butzow T, Laughin GA y col. 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.
  29. Venturoli J, Porcu E, Fabbri R y col. Longitudinal evaluation of the different gonadotropin pulsatile patterns in anovulatory cycles of young girls. J. Clin. Endocrinol. Metab. 1992; 74:836-841.
  30. Ibáñez L, De Zegher F, Potau N. Anovulation after precocious pubarche: early markers and time course in adolescence. J. Clin. Endocrinol. Metab. 1999; 84:2691-2695.
  31. Franks S, Robinson S, Willis DS. Nutrition, insulin and polycystic ovary syndrome. J. Reprod. Fertil. 1996; 1:47-53.
  32. Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17-alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N. Engl. J. Med. 1996; 335:617-623.
  33. Sir Petermann T, Rabenbauer B, Wildt L. The effect of Flutamide on pulsatile gonadotrophin secretion in hyperandrogenemic women. Hum. Reprod. 1993; 8:1807-1812.
  34. Sir Petermann T, Muñoz A, Candia M y col. LH secretion by the female pituitary: effect of testosterone and the blockade of its receptor. Exp Clin Endocrinol 1996; 104 (Suppl 1):20-22.
  35. Sir Petermann T, Castillo T, Muñoz S y col. Prueba de tolerancia a la insulina. Un método útil para determinar resistencia insulínica en mujeres hiperandrogénicas obesas. Rev. Méd. Chile. 1996; 124:931-937.
  36. Sir Petermann T, López G, Castillo T y col. Marcadores bioquímicos y métodos de cuantificación de insulino resistencia en mujeres normales, obesas e hiperandrogénicas. Rev. Med. Chile. 1997; 125:977-985.
  37. Sir Petermann T, López G, Castillo T y col. Naltrexone effects on insulin sensitivity and insulin secretion in hyperandrogenic women. Exp. Clin. Endocrinol. Diabetes 1998; 106:389-394.
  38. Burghen GA, Givens JR, Kitabchi AE. Correlation of hyperandrogenism with hyperinsulinemia in polycystic ovarian disease. J. Clin. Endocrinol. Metab. 1980; 50:113-116.
  39. Nestler JE, Strauss JF III. Insulin as an effector of human ovarian and suprarrenal steroid metabolism. Endocrinol. Metab. Clin. North. Am. 1991; 20:807-832.
  40. Franks S, Gilling-Smith C, Watson H y col. Insulin action in the normal and polycystic ovary. Endocrinol. Metab. North. Am. 1999; 28:361-378.
  41. Morimoto S, Fernandez-Mejia C, Romero-Navarro G y col. Testosterone effect on insulin content, messenger ribonucleic acid levels, promoter activity, and secretion in the rat. Endocrinology 2001; 142:1442-1447.
  42. Dunaif A, Segal KR, Futterweit W y col. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989; 38:1165-1174.
  43. Dunaif A, Segal KR, Shelley DR y col. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes 1992; 41:1257-1266.
  44. Dunaif A, Xia J, Book C y col. Excessive insulin receptor serine phosphorilation in cultured fibroblast and skeletal muscle: A potential mechanism for insulin resistance in the polycystic ovary syndrome. J. Clin. Invest. 1995; 96:801-810.
  45. Dunaif A. Hyperandrogenic anovulation (PCOS): A unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus. Am. J. Med. 1995; 98 (Suppl 1A):33S-39S.
  46. Barnes RB, Rosenfield RL, Ehrmann DA y col. Ovarian hyperandrogenism as a result of congenital suprarrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women. J .Clin. Endocrinol. Metab. 1994; 79:1328-1333.
  47. Clarke IJ, Scaramuzzi RJ, Short RV. Ovulation in prenatal androgenized ewes. J Endocrinol 1977; 73:385-389.
  48. Dumesic DA, Abbott DH, Eisner JR y col. Prenatal exposure of female rhesus monkeys to testosterone propionate increases serum luteinizing hormone levels in adulthood. Fertil. Steril. 1997; 67:155-163.
  49. Eisner JR, Dumesic DA, Kemnitz JW y col. Timing of prenatal androgen excess determines differential impairment in insulin secretion and action in adult female rhesus monkeys. J. Clin. Endocrinol. Metab. 2000; 85:1206-1210.
  50. Eisner JR, Barnett BA, Dumesic DA y col. Ovarian hyperandrogenism in adult female rhesus monkeys exposed to prenatal androgen excess. Fertil Steril 2002; 77:167-172.
  51. Birch RA, Padmanabhan V, Foster DL y col. Prenatal programming of reproductive neuroendocrine function: fetal androgen exposure produces progressive disruption of reproductive cycles in sheep. Endocrinology 2003; 144:1426-1434.
  52. Rosser C, Herkimer C, Sarma HN, Recabarren SE y col. Fetal programming: prenatal exposure to excess testosterone programs hyperinsulinemia. Biol Reprod 2003; 68(Suppl 1):293 (Abstract 440).
  53. Recabarren SE, Sir Petermann T, Lobos A y col. Altered insulin sensitivity indices at early postnatal age following prenatal testosterone exposure. 86th Endocrine Meeting of the Endocrine Society, USA, Abstract P2-73, New Orleans, USA, 16-19 June, 2004
  54. Sir Petermann T, Maliqueo M, Angel B. Maternal serum androgens in pregnant women with polycystic ovary syndrome: possible implications in prenatal androgenization. Hum Reprod. 2002; 17:2573-2579.
  55. Kosut SS, Wood RI, Herbosa-Encarnacion C y col. Prenatal androgens time neuroendocrine puberty in the sheep: effect of testosterone dose. Endocrinology 1997; 138:1072-1077.
  56. Nestler JE. Insulin and insulin-like growht factor I stimulate the 3beta-hydroxisteroid dehydrogenase activity of human placental cytotrophoblast. Endocrinology 1989; 125:2127-2133.
  57. Nestler JE. Insulin-like growht factor II is a potent inhibitor of the aromatase activity of human placental cytotrophoblast. Endocrinology 1990; 127:2064-2070.
  58. Abbott DH, Dumesic DA, Franks S. Developmental origin of polycystic ovary syndrome - a hypothesis. J Endocrinol. 2002; 174:1-5.
  59. Glueck CJ, Goldenberg N, Wang P y col. Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy. Hum Reprod. 2004; 19:510-521.

 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618