Suppression of Urinary and Plasma Follicle-Stimulating Hormone by Exogenous Estrogens in Prepubertal and Pubertal Children

Abstract

A B S T R A C T Clomiphene citrate, an "anti-estrogen" with mild estrogenic properties, inhibits rather than stimulates gonadotropin excretion in prepubertal and early pubertal children. These and other data suggest that the sensitivity of the hypothalamic-pituitary "gonadostat" decreases at the onset of puberty. To test this hypothesis further, the daily excretion of urinary folliclestimulating hormone (FSH) and luteinizing hormone (LH) was determined in 19 children (5 "short normals" and 14 with isolated human growth hormone (HGH) deficiency) who were given ethinyl estradiol (EE) 1.4-14.7 Ag/m2 per day (2-10 Ag/day) for 4 to 7 days. In addition, plasma and urinary gonadotropins and plasma estrogens were serially determined in two prepubertal females( with isolated HGH deficiency) given two injections (24 h apart) of estradiol benzoate, 10 isg/kg.FSH and LH concentrations in plasma and kaolin-acetone urinary concentrates and plasma 173-estradiol (E2) and estrone (El) were measured by radioimmunoassays. 2-3 Ag/m2 per day of EE significantly suppressed urinary FSH (and LH when detected in the control period) in two out of six prepubertal children, while all doses > 5 ,ug/m2 per day suppressed urinary gonadotropins to undetectable levels in eight prepubertal subjects. In early to midpubertal subjects, 2-10 Ag/m2 per day of EE produced a slight suppression of urinary FSH, but failed to suppress to undetectable levels. gonadotropins remained suppressed for the duration of the study (3 days). Plasma E2 and Ei rose from prepubertal values to peak concentrations of 150 to 250 pg/ml (E2), and 50 and 100 pg/ml (Ei) at approximately 36 h. We conclude that the hypothalamic-pituitary-gonadal axis is operative in the prepubertal child and that the sensitivity of the hypothalamic-pituitary center(s) which control the secretion of FSH and LH decreases at the onset of puberty in man. INTRODUCTIONMounting evidence suggests that the gonads in the prepubertal human being are not quiescent and, in fact, play a significant role in regulating the release of gonadotropins (1-4). Previous reports from this laboratory (5, 6) demonstrated that clomiphene citrate, an "anti-estrogen" with mild estrogenic properties, suppresses the excretion of urinary follicle-stimulating hormone (FSH) in prepubertal children. As little as 1 mg/m2 per day of oral clomiphene citrate decreases

Timing and completion of puberty in female mice depend on estrogen receptor α-signaling in kisspeptin neurons

“…A role for ERα in ARC kisspeptin neurons in puberty onset in this species may therefore figure less importantly, although it is possible that central ERs are activated in a ligand-independent manner (28) by peripheral and central signals in prepubertal monkeys, thereby constituting an estrogen-independent, yet estrogen receptor-dependent, mechanism for the pubertal restraint. Estrogen treatments suppress gonadotropin secretion more effectively in prepubertal girls than in adult women (29), allowing for the possibility that some steroid-dependent mechanism may contribute to the timing of puberty onset in human females.…”

Responsivity of Pituitary Gonadotropes to Luteinizing Hormone-releasing Factor in Idiopathic Precocious Puberty, Precocious Thelarche, Precocious Adrenarche, and in Patients Treated with Medroxyprogesterone Acetate

“…It would seem that before puberty the hypothalamic gonadostat is highly sensitive to negative feedback by sex steroids (1 3, 18); as a consequence of the diminished endogenous LRF secretion, there is little stimulation of the prepubertal LH-secreting gonadotropes and, hence, less readily releasable pituitary LH. With the onset of puberty and progression t o adulthood, neural inhibition of LRF secretion is reduced as a result of decreasing sensitivity to gonadal steroid negative feedback (13,18,21) so that pituitary gonadotropin synthesis and reserve increases. In addition, increased pituitary responsivity to L R F during puberty may be modulated by the rising levels of gonadal sex steroids.…”

The Role of Blood Spot Dehydroepiandrosterone Sulfate Levels in Adjunct to Hand Wrist Radiographs as Skeletal Maturity Indicator

“…Systemic factors include growth hormone (GH), insulin-like growth factor 1 (IGF-1), thyroid hormones, and sex steroids. An increase in gonadotropin secretion consequent to the maturation of the central nervous system pituitary system plays a critical role in the initiation of puberty (11,12).…”