Delayed Effects of in Vivo LHRH Immunoneutralization on Gonadotropins and Prolactin Secretion in the Female Rat

A single ip injection (0.2 ml) of a rabbit antiserum to LHRH was given at noon on proestrus (day 0) to 4-day cycling rats. A blockade of the preovulatory surge of LH and FSH was observed, as well as inhibition of ovulation; the prolactin (PRL) surge was unaffected. Four days later, palsma LH and FSH were still low and hypoprolactinemia appeared, while the estrous cycle was unaffected. Then, after a transient diestrous period, vaginal smears indicated a pattern of persistent estrus for at least 240 days starting from day 8 after treatment. Hypothalamic LHRH remained low throughout this period, with the exception of a transient rise around day 36; hypothalamic serotonin and dopamine were unchanged. A peak of FSH in serum appeared on day 28 and an elevation of serum LH on day 36; this latter rise was concomitant with the increase of hypothalmic LHRH and with ovarian luteinization. Except for this short period, the ovaries showed a picture of persistent estrus, with large, cystic follicles. During the whole experimental period, basal serum FSH levels were higher than those of LH. Pituitary FSH and LH contents remained in the range usually found during the normal estrous cycle. Starting from the 8th day after treatment, a marked hyperprolactinemia appeared. Serum estradiol and progesterone were assayed on days 10 and 40 after injection; no significant increase in either steroid was observed on day 10, but on day 40 the levels of estradiol increased to values similar to those of progestrus, while progesterone showed only a small, but significant, increase. Thus, a single injection of LHRH antiserum (AS) in a normal cycling rat provoked a long-term alteration in hypothalamic function. The results so far obtained suggest that the long-lasting hyperprolactinemia induced by this treatment, might be due to an abnormal ovarian secretion.