Gonadotropin and testosterone secretion in normal human males after stimulation with gonadotropin-releasing hormone (GnRH) or potent GnRH analogs using different modes of application.

Gonadotropin-releasing hormone (GnRH) and some potent long-acting GnRH analogs, applied by different routes of administration, were tested in six healthy human males. The effects on gonadotropin secretion were compared with the one after intravenous (i.v.) bolus injection of 25 microgram of GnRH. The net increase of luteinizing hormone (deltaLH) in serum produced by 25 microgram of GnRH i.v. was matched by subcutaneous (s.c.) injection of 100 microgram of GnRH, dissolved in 20% gelatin or without gelatin; 5 microgram of D-Ser (TBU)6-des-Gly10-GnRH-ethylamide i.v.; 5 microgram of D-Leu6-des-Gly10-GnRH-ethylamide i.v.; and 50 microgram of D-Trp6-des Gly10-GnRH-ethylamide given pernasally (p.n.). D-Leu6-des-Gly10-GnRH-ethylamide, 50 microgram p.n., produced one-half such increase as did also multiple p.n. administrations of 200 microgram of GnRH every 2 hours. With 100 microgram of GnRH and all analogs, elevation of serum LH lasted for about 7 to 9 hours. The longest elevation was observed with GnRH dissolved in gelatin and with D-Ser (TBU)6-des-Gly10-GnRH-ethylamide, as reflected by the greatest areas under the curves of net increase. The longer the duration of the action of LH secretion, the higher was the observed increase in follicle-stimulating hormone (FSH). Correlation between effect on LH secretion and testosterone secretion was not found. By infusion of 1 microgram/kg/hour od D-Leu6-des-Gly10-GnRH-Ethylamide in two men over a period of 15 hours, a plateau of gonadotropin levels was reached within 7 to 9 hours. These plateau levels, especially of FSH, were higher than after bolus injection or p.n. application.