Daily GnRH agonist treatment delays the development of reproductive physiology and behavior in male rats.

ABSTRACT

The present study was designed to examine the effects of suppressing pubertal onset with leuprolide acetate, a gonadotropin releasing hormone (GnRH) agonist. Starting on postnatal day (PD) 25, male Long-Evans rats were injected daily with either leuprolide acetate (25 µg/kg dissolved in 0.9% sterile physiological saline; n = 13) or sterile physiological saline (1.0 ml/kg 0.9% NaCl; n = 14) for a total of 25 days. Males were monitored daily for signs of puberty (i.e., preputial separation). On the last day of leuprolide treatment (PD 50), half of each treatment group was injected with 10.0 µg of estradiol benzoate (EB) daily for three consecutive days (PD 50-52) and 1.0 mg of progesterone (P) on the 4th day (PD 53), whereas the other half of each treatment group received oil injections. Four hours after P injections, all subjects were given the opportunity to interact with a gonadally-intact male and a sexually receptive female rat (i.e., a partner-preference test with and without physical contact). Copulatory behavior and sexual motivation were measured. Hormone injections and mating tests were repeated weekly for a total of 3 consecutive weeks. Results showed that leuprolide delayed puberty as well as the development of copulatory behavior and the expression of sexual motivation. By the last test, the leuprolide-treated subjects showed signs of catching up, however, many continued to be delayed. Estradiol and progesterone mildly feminized male physiology (e.g., decreased testes weight and serum testosterone) and behavior (e.g., increased lordosis), but did not interact with leuprolide treatment.