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The Rapid Ovarian Secretory Response to Pituitary Stimulation by the Gonadotropin-Releasing Hormone Agonist Nafarelin in Sexual Precocity^*

ROBERT L. ROSENFIELD, LUIGI R. GARIBALDI, GEORGE W. MOLL, JR., ALBERT C. WATSON and STEPHEN BURSTEIN

Departments of Pediatrics and Medicine, University of Chicago Pritzker School of Medicine Chicago, Illinois 60637

Address requests for reprints to: Robert L. Rosenfield, M.D., Wyler Children's Hospital, 5841 South Maryland Avenue, Chicago, Illinois 60637.

We evaluated a GnRH agonist (GnRHa) asa potential single stimulus to both pituitary and ovarian secretion i n 13 girls with true precocious puberty. We compared the GnRH agonist [6-D-(2-naphthyl)alanine]GnRH acetate (nafarelin, Syntex) administered as a single sc injection of 0.2µg/kg to GnRH infused iv in a dose ofµg/kg-h for3h and assessed the response of plasma steroid intermediates in estradiol (E2) bio synthesis.

Although serum LH and FSH levels increased to similar peaks 3 h after commencing GnRH and nafarelin testing, they rose faster (P<0.01 at 1h)and remained elevated longer (PP< 0.05 at 24 h) after nafarelin administration. At the third hour of testing with either agent, LH and FSH rose 8.8- and 3.4-fold, respectively (P < 0.001 vs. baseline), whereas the rise in E2 was inconsistent and averaged only one third (P < 0.02). However, plasma E2 increased later after nafarelin, but not after GnRH, rising from a baseline level of 30 ± 6 (±SEM) to 115± 13pg/ml at 24h (P < 0.001). The least E2 response to nafarelin at this time was 150%. This rise is probably an underestimate of the maximum E2 rise, since a 6-fold response to nafarelin was found at 12 h in patients sampled then.

Measurement of steroid intermediates from progesterone and 17-hydroxypregnenolone to E2 indicated that the response to nafarelin was typical of normal ovarian follicular secretion. That is, plasma levels of the intermediates in E2 biosynthesis rose less than 2-fold, and only the elevations in androstenedione, from 58 ± 10 to 78 ± 16 ng/dl (P < 0.05), and estrone, from 14 ± 3 to 38 ± 7 pg/ml (P < 0.02), at 24h were significant.

The greater effectiveness of nafarelin than GnRH in stimulating E2 secretion appears to be related to the more prolonged gonadotropin response. The magnitude, consistency, specificity, and rapidity of the gonadotropin and E2 responses to nafarelin indicate that this is a promising agent for rapidly testing pituitary and ovarian function simultaneously. (J Clin Endocrinol MetabGS 63: 1386, 1986)

^* Presented in preliminary form at the Annual Meetings of the American Pediatric Society (May 4, 1986) and The Endocrine Society (June 24, 1986). This work was supported in part by USPHS Grants HD-06308 and RR-00305 and Syntex Research.

Present address: Emory University School of Medicine, Department of Pediatrics, 2040 Ridgewood Drive N.E., Atlanta, Georgia 30322.

Received June 6, 1986.