title: Exaggerated 17-hydroxyprogesterone response to intravenous infusions of recombinant human LH in women with polycystic ovary syndrome.
abstract: Studies using pharmacological gonadotropin stimulation suggest that ovarian steroidogenesis is abnormal in the polycystic ovary syndrome (PCOS). We assessed ovarian steroid secretion in response to near-physiological gonadotropin stimuli in 12 ovulatory controls and 7 women with PCOS. A gonadotropin-releasing hormone-receptor antagonist (ganirelix, 2 mg sc) was given to block endogenous LH secretion, followed by dexamethasone (0.75 mg orally) to suppress adrenal androgen secretion. After ganirelix injection (12 h), intravenous infusions of recombinant human LH (0, 10, 30, 100, and 300 IU; each over 8 min) were administered at 4-h intervals in a pseudorandomized (highest dose last) manner. Plasma LH, 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone were measured concurrently. LH dose-steroid response relationships (mean sex-steroid concentration vs. mean LH concentration over 4 h postinfusion) were examined for each subject. Linear regression of 17-OHP on LH yielded a higher (mean +/- SE) slope in PCOS (0.028 +/- 0.010 vs. 0.005 +/- 0.005, P < 0.05), whereas extrapolated 17-OHP at zero LH was similar. The slopes of other regressions did not differ from zero in either PCOS or controls. We conclude that near-physiological LH stimulation drives heightened 17-OHP secretion in patients with PCOS, suggesting abnormalities of early steps of ovarian steroidogenesis. With the exception of 17-OHP response in PCOS, no acute LH dose-ovarian steroid responses were observed in controls or PCOS. Defining the precise mechanistic basis of heightened precursor responsiveness to LH in PCOS will require further clinical investigation.
authors.affiliation: Center for Research in Reproduction, Division of Endocrinology, Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA. cm2hq@virginia.edu
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McCartney
authors.forename: Amy B
authors.initials: AB
authors.lastname: Bellows
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Gingrich
authors.forename: Yun
authors.initials: Y
authors.lastname: Hu
authors.forename: William S
authors.initials: WS
authors.lastname: Evans
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood*; D000328:Adult; D015992:Body Mass Index; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006727:Hormone Antagonists / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007986:Luteinizing Hormone / Q000008:administration & dosage*; D010053:Ovary / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000188:drug therapy*; D020551:Pulse Therapy, Drug; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D005300:Fertility Agents, Female; D006727:Hormone Antagonists; D011966:Receptors, LHRH; D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone; D019326:17-alpha-Hydroxyprogesterone; D007986:Luteinizing Hormone; C061018:ganirelix