Inhibition of pituitary-gonadal axis in mice by long-term administration of D-Trp-6-LHRH microcapsules.

Female mice were injected, every 30 days for 5 months, with a long-acting formulation of microcapsules liberating 2.5 micrograms D-Trp-6-LHRH/day. The control group was injected with vehicle only. At 30 days after the last injection mice were killed, ovaries, uteri and adrenals were weighed and fixed in formalin for histological studies. LH and oestradiol concentrations were measured by RIA. In the D-Trp-6-LHRH-treated group, the weights of the ovaries and uterus (P less than 0.01 and P less than 0.05, respectively), and LH and oestradiol values (P less than 0.02 and P less than 0.01, respectively) were reduced compared to controls. Histologically, the ovaries contained a large number of degenerated, atretic follicles, and corpora lutea had almost completely disappeared. These results indicate, contrary to the prevailing opinion, that mice are sensitive to inhibitory effects of LHRH agonists and that a suppression of the pituitary-gonadal axis can be obtained with long-term administration of D-Trp-6-LHRH microcapsules.