Changes in pituitary LHRH receptor levels in situations of increased or decreased gonadotrophin secretion in the male rat

Anterior pituitary LHRH receptor numbers were studied by measuring binding of ¹²⁵I-labelled (d-Ser-Bu^t)⁶-des-Gly¹⁰ LHRH ethylamide in male rats in which gonadotrophin output is markedly altered. Rats made hyperprolactinaemic by transplantation of 2 pituitary glands under the kidney capsule 98 days previously had significantly lower pituitary contents and serum levels of LH and FSH than controls, although serum concentrations of testosterone remained within the normal range. Pituitary LHRH receptor numbers in these animals were significantly reduced. A condition of further suppression of pituitary contents and serum levels of LH and FSH was achieved by active immunization against LHRH for one year, which also reduced serum concentrations of testosterone to non-detectable levels. This was associated with a marked reduction in LHRH receptor numbers. In contrast, rats castrated 49 days previously demonstrated the expected marked rise in pituitary content and serum levels of LH and FSH and had a marked rise in the number of pituitary LHRH receptors. Castration of animals with pituitary transplants resulted in a similar response. Rats in which testosterone was neutralized by active immunization also showed an increase in pituitary contents and serum levels of LH and FSH, but these changes were lower than in castrated rats, probably owing to the presence of small amounts of non-antibody-bound testosterone. These animals had only a marginal rise in pituitary LHRH receptor numbers.Our results, showing a lowering in LHRH receptors when hypothalamic LHRH stimulation of the pituitary is thought to be reduced (hyperprolactinaemia and LHRH immunization) and an elevation in receptors when LHRH output is thought to be increased (castration and testosterone immunization), add further support to the view that LHRH regulates its own receptors.