Accelerated 24-hour luteinizing hormone pulsatile activity in adolescent girls with ovarian hyperandrogenism: relevance to the developmental phase of polycystic ovarian syndrome.
A study was initiated to delineate the neuroendocrine characteristics of hyperandrogenic adolescent girls with the aim of discerning features that may relate to the pubertal onset of the polycystic ovarian syndrome. Thirteen 11- to 18-yr-old girls with mild to moderate signs of hyperandrogenism (HA) and increased ovarian volume and 28 age-matched normal girls were recruited for the study. LH pulsatility and FSH levels were analyzed based on serum concentrations measured with sensitive immunofluorometric assays in samples taken at 10-min intervals for 24 h under basal conditions, GnRH antagonist (Nal-Glu) suppression, and dexamethasone suppression. Adrenal and ovarian contributions to serum cortisol, dehydroepiandrosterone, androstenedione, testosterone (T), estrone (E1), estradiol (hourly), 17-hydroxypregnenolone, and 17-hydroxyprogesterone (17PO) concentrations were compared during basal and suppression conditions and after gonadotropin and adrenal stimulations by bolus GnRH (10 micrograms) and CRF (1 microgram/kg). The progression from sleep-augmented pulsatile LH secretion to higher LH levels during wake than sleep observed during normal pubertal development occurred 2 yr earlier in the HA group. The number of LH pulses was significantly higher in the HA group during both sleep and waking, whereas pulse amplitude was higher only during the awake time. Thus, mean LH was 2.0-fold higher during the awake time and only 1.6-fold higher during sleep in the HA group compared to the normal group. The elevation of FSH in HA was small relative to that of LH, resulting in an increased LH/FSH ratio (P < 0.008). The HA group had higher concentrations of 17PO (1.8-fold), androstenedione (1.9-fold), T (2.4-fold), and E1 (1.7-fold) than the normal group (all P < 0.001), with no alteration in circadian rhythm. These elevated steroid levels were significantly correlated with LH levels in the basal state and decreased in proportion to the change in LH during Nal-Glu suppression. During adrenal suppression with dexamethasone, concentrations of cortisol, dehydroepiandrosterone, and 17-hydroxypregnenolone decreased in both groups (P < 0.001), but significant suppression of 17PO, T, and E1 occurred only in the normal girls, indicating the ovarian origin of the increased levels of these steroids with enhanced expression of 17 alpha-hydroxylase activity in HA girls.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Reproductive Medicine, University of California-San Diego School of Medicine, La Jolla 92093-0802.
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D000293:Adolescent; D000735:Androstenedione / Q000097:blood; D002648:Child; D002940:Circadian Rhythm; D003907:Dexamethasone; D004970:Estrone / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D006801:Humans; D017588:Hyperandrogenism / Q000473:pathology / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D010053:Ovary / Q000473:pathology / Q000503:physiopathology*; D010507:Periodicity; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology*; D011627:Puberty; D013739:Testosterone / Q000097:blood
C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D004970:Estrone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D000735:Androstenedione; D003907:Dexamethasone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone