title: Corticotropin-releasing hormone: a potent androgen secretagogue in girls with hyperandrogenism after precocious pubarche.
abstract: CRH is an adrenal androgen secretagogue in men and has been proposed as a candidate regulator of adrenarche. CRH also affects androgen production by theca cells and may be involved in the pathogenesis of ovarian hyperandrogenism (OH). Precocious pubarche (PP) in girls can precede adolescent OH, a condition characterized by a high ovarian 17-hydroxyprogesterone (17-OHP) response 24 h after GnRH agonist challenge. In adolescent girls with a history of PP, we assessed the early androgen response to CRH, as well as the CRH effect on the late ovarian response to GnRH agonist. Within a randomized cross-over design, saline or CRH (human CRH 1 microg/kg x h in saline) was infused over 3-h (1100-1400 h) into 12 adolescent girls (age 17+/-2 yr; body mass index 21.4+/-0.9 Kg/m2) who had been pretreated with dexamethasone (1 mg at 0 h) and GnRH agonist (leuprolide acetate 500 microg sc at 0800 h = time 0). All adolescents had hirsutism, irregular menses, hyperandrogenemia, and hyperinsulinemia after PP. Serum LH, FSH, androstenedione, dehydroepiandrosterone (DHEA), and DHEA-sulfate (DHEAS) were measured at time 0, 3, 6, and 24 h, and ACTH and 17-OHP were measured at time 0, 6, and 24 h. ACTH concentrations at the end of saline or CRH infusions were less than 45 pg/mL; neither saline nor CRH infusions evoked early changes in 17-OHP levels. Within 3 h of CRH infusion, DHEAS increased by 46%, on average; androstenedione increased 2.5-fold and DHEA increased 5-fold duringCRH infusion (all P < 0.0001 compared with saline). There was no detectable CRH effect on the responses of LH, FSH, DHEA, DHEAS, 17-OHP, androstenedione, testosterone, and estradiol 24 h after GnRH agonist administration; five of 12 girls had elevated 17-OHP responses suggestive of OH. In conclusion, CRH was found to be a potent adrenal androgen secretagogue in adolescent girls with hyperandrogenism after PP. In this study, CRH failed to detectably affect the ovarian androgen response to gonadotropins.
authors.affiliation: Hospital Sant Joan de Déu, University of Barcelona, Spain. lourdes.ibanez@deinfo.es
authors.forename: L
authors.initials: L
authors.lastname: Ibáñez
authors.forename: N
authors.initials: N
authors.lastname: Potau
authors.forename: M V
authors.initials: MV
authors.lastname: Marcos
authors.forename: F
authors.initials: F
authors.lastname: de Zegher
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000728:Androgens / Q000378:metabolism*; D015992:Body Mass Index; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D003907:Dexamethasone; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005938:Glucocorticoids; D006801:Humans; D017588:Hyperandrogenism / Q000209:etiology / Q000503:physiopathology*; D016729:Leuprolide; D007986:Luteinizing Hormone / Q000097:blood; D011629:Puberty, Precocious / Q000150:complications*
chemical_list: D000728:Androgens; D005938:Glucocorticoids; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003346:Corticotropin-Releasing Hormone; D016729:Leuprolide