Possible role of histamine in the regulation of secretion of luteinizing hormone in the ewe

Concentrations of histamine were quantified by an enzymatic isotopic assay in different regions of the brain and pituitary gland of gonadal-intact and chronically ovariectomized ewes during the anestrous season. Sera concentrations of LH were confirmed to be elevated in ovariectomized compared with intact animals immediately before tissues were obtained. Areas of the brain that were examined included cerebral cortex, thalamus, pineal gland, hypothalamus (rostral, medial basal, median eminence), midbrain, cerebellum and brain stem. Concentrations of histamine were greatest within the thalamus, pineal gland, medial basal hypothalamus and median eminence. Histamine within the medial basal hypothalamus was greater (P less than .05) in ovariectomized than in ovarian-intact animals. Further experiments were designed to determine the effect of antihistaminic drugs on secretion of LH. Ovariectomized ewes were treated every 6 h (i.m.) for 24 h with diphenhydramine (an antagonist of the H1-receptor for histamine), cimetidine (an H2-receptor antagonist), a combination of the drugs, or vehicle. Twelve hours after initiation of treatments, animals were injected with estradiol. Diphenhydramine depressed (P less than .01) basal serum concentrations of LH and the positive feedback effect of estradiol on serum concentrations of LH. Cimetidine did not influence the pattern of secretion of LH. Diphenhydramine did not alter LHRH-induced release of LH in ovariectomized ewes or basal serum concentrations of LH in ovarian-intact anestrous ewes. We suggest that histamine acts at the level of the central nervous system through an H1-receptor mechanism to control secretion of LH in female sheep.