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Pharmacodynamics of Gonadotropin-Releasing Hormone (GnRH). II. Pattern of GnRH Delivery Alters Pituitary Luteinizing Hormone Secretion in Women^*

DAVID J. HANDELSMAN and LYN M. BOYLAN

Departments of Medicine and Obstetrics and Gynecology, University of Sydney Sydney 2006
The Andrology Unit, Royal Prince Alfred Hospital Camperdown, Sydney 2050, Australia

Address all correspondence and requests for reprints to: Dr. David J Handelsman, Department of Medicine, University of Sydney, Sydney 2006, Australia.

The pulse frequency, amplitude, and mode of administration of GnRH all influence gonadotropin secretion and, ultimately, pituitary-gonadal function. We studied plasma LH responses to repetitive iv administration of GnRH given hourly for 5 h as a 2-µg rapid (<15 s) bolus dose or a 2-µg dose infused for 15 min of each hour in seven women deficient in endogenous GnRH and sex steroids. Plasma LH levels, measured at 10-min intervals throughout the 5-h period, rose more briskly (pattern x time course interaction: F = 3.33; P < 0.0001) to higher levels overall (F = 11.7; P = 0.014) after rapid bolus GnRH administration than after GnRH infusion. Plasma FSH levels increased during both modes of delivery, with higher responses to rapid bolus GnRH administration (P = 0.005). Plasma estradiol levels did not change during either 5-h study. We conclude that the pattern of delivery of GnRH is a determinant of pituitary LH and FSH secretion in untreated hypogonadotropic women, and therefore, that alterations in the GnRH wave form and/or peak plasma GnRH concentrations consequent upon different rates of GnRH entry into the bloodstream may explain the different responses that occur when GnRH is given by different routes.

^* This work was supported by the Wellcome Australia Trust. Presented in part at the 30th Annual Meeting of The Endocrine Society of Australia, 1987 (Abstract 65).

Wellcome Senior Research Fellow.

Received October 6, 1987.