GnRH agonist stimulation of the pituitary-gonadal axis in children: age and sex differences in circulating inhibin-B and activin-A.
BACKGROUND
Inhibin-B decreases and activin increases FSH secretion in adults. We investigated whether an FSH-inhibin/activin feedback loop exists before or during puberty.


METHODS
FSH secretion was stimulated with 10 microg/kg leuprolide acetate (GnRH agonist) in 18 girls, ages 1.0-13.2 years, and 11 boys, ages 8.9-15.2 years, with variations in pubertal development, and in five normal 9- to 10-year-old girls. Blood, obtained at 0, 0.5, 1, 2, 4, 8, 12, 16, 20 and 24 h after GnRH agonist, was analysed for LH, FSH, activin-A, inhibin-A, inhibin-B, follistatin 288 and estradiol/testosterone.


RESULTS
FSH increased within 30 min of GnRH agonist administration with a peak greater in girls than boys (P=0.0006). Baseline inhibin-B was greater in boys than girls (P=0.01), while baseline activin-A concentrations were greater in girls. GnRH agonist-stimulated FSH increased inhibin-B in girls by 8 h and in boys by 20 h (P<0.05), but did not affect activin-A. Inhibin-B increases were seen only in girls older than 5 years.


CONCLUSIONS
An inhibin-B-FSH feedback loop exists prior to the onset of puberty in girls older than 5 years. Sex differences in activin-A and inhibin-B concentrations may be responsible for sex differences in serum FSH concentrations.
Elsholz
Daniel D
DD
Department of Pediatrics, Division of Endocrinology, University of Michigan, Ann Arbor, MI 48109-0646, USA.
Padmanabhan
Vasantha
V
Rosenfield
Robert L
RL
Olton
Pamela R
PR
Phillips
David J
DJ
Foster
Carol M
CM
D028341:Activins / Q000097:blood* / Q000187:drug effects; D000293:Adolescent; D000367:Age Factors; D001846:Bone Development / Q000502:physiology; D002648:Child; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006066:Gonads / Q000187:drug effects* / Q000502:physiology; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy; D006801:Humans; D028322:Inhibin-beta Subunits / Q000097:blood* / Q000187:drug effects; D007265:Inhibins / Q000097:blood* / Q000187:drug effects; D016729:Leuprolide / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D011627:Puberty; D011629:Puberty, Precocious / Q000097:blood / Q000188:drug therapy; D012016:Reference Values; D012727:Sex Characteristics
C422405:activin A; C422364:inhibin B; D028341:Activins; D007987:Gonadotropin-Releasing Hormone; D007265:Inhibins; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits; D016729:Leuprolide