Desensitization of the pituitary gland induced in vivo by luteinizing hormone-releasing hormone (LRH) or by the LRH-analogue buserelin does not affect the autonomous secretion of luteinizing hormone and follicle stimulating hormone as observed in vitro

Abstract. Three-weeks ovariectomized rats were sc implanted with Alzet® osmotic minipumps which released either LRH or the LRH-analogue buserelin at the rate of 250 ng/h. Control rats were implanted with a silastic 'shampump'. After explantation, 6 days later, the pituitary glands of part of these rats were exposed to the maximally active LRH concentration of 1 μg/ml for a period of 6 h. using a perifusion system. In a second group of rats explantation and perifusion was done not directly, but 5 days after cessation of the I.RH pretreatment. After 6 days in vivo pre-treatment with LRH or with buserelin the pituitary LH and FSH stores were partially depleted, the depletion after buserelin being stronger than after LRH. The pituitary glands of the first group of rats showed rates of both maximally LRH-stimulated and unstimulated (autonomous) LH- and FSH-secretion which were strongly impaired, the impairment after buserelin being stronger than after LRH. In the group with a 5 days interval between in vivo LRH/buserelin pre-treatment and explantation the pituitary LH and FSH stores were restored to the range of pre-treatment levels. Of these pituitaries the autonomous secretion of LH and FSH as well as the maximally LRH-stimulated secretion of FSH was restored to the normal level; the maximally LRH-stimulated secretion of LH, however, remained depressed, indicating that 5 days after cessation of exposure to LRH or to buserelin, and in spite of restored pituitary LH/FSH contents, the sensitivity of the LH releasing system to LRH was still subnormal. The results suggest that the autonomous secretion of LH and FSH as well as the LRH-stimulated secretion of FSH, but not the LRH-stimulated secretion of LH may be dependent on the content of the pituitary LH and FSH stores. Furthermore, after treatment with LRH or buserelin the autonomous secretion of LH may return to a normal level when the sensitivity of the LH releasing system to LRH is still impaired: apparently, the mechanisms underlying the autonomous and the LRH-stimulated LH secretion do not influence each other. It is discussed that in situations in which a complete suppression of the pituitary-gonadal axis is demanded (carcinomata of the breast or the prostate; precocious puberty) desensitization of the pituitary gland with super-active LRH-analogues like buserelin alone is not sufficient, as this does not affect the autonomous secretion of LH and FSH. For total suppression of gonadal activity the pituitary gland must be completely depleted with relatively large doses of analogue.