EFFECTS OF CASTRATION ON LUTEINIZING-HORMONE AND FOLLICLE-STIMULATING-HORMONE SECRETION BY PITUITARY-CELLS FROM MALE-RATS

Because the role of the pituitary in the testicular control of gonadotropin secretion remains controversial, we examined the effectsof castration on the release of LH and FSH under basal conditions and in response to GnRH stimulation by dispersed pituitary cells in monolayer culture as well as by cells perifused with pulses of GnRH. These effects were compared to changes in LHβ, FSHβ, and a-subunit mRNA levels determined by Northern blot analysis. Pituitary cells were prepared from 7-week-old intact rats and rats orchidectomized 2 weeks previously. Castration increased basal FSH secretion from monolayer cultures, interpulse FSH release from perifused pituitary cells, FSHβ mRNA concentrations and serum FSH levels each approximately 2-fold, whereas pituitary FSH contents were similar in cells from intact and castrated rats. Pituitary LH content rose 3-fold, LHβ mRNA rose 5.6-fold, and basal LH secretion increased 6-fold, but serum LH levels increased 22-fold. Thus, the change in FSH synthesis inferred from the increase in FSHβ mRNA was proportional to the increase in FSH secretion both in vitro and in vivo. Whereas the basal release of LH in vitro was also proportional to the change in LHβ mRNA, secretion of LH in vivo exceeded these changes, underscoring the importance of increased GnRH to the serum LH castration response. Castration resulted in an increase in the sum of FSH content and secretion during 10 days in culture in the absence of GnRH, indicating ongoing FSH synthesis. Total LH declined in cells from intact rats, and this decline was prevented by castration; this effect may be due to a castration-related decrease in intracellular LH degradation or increased LH synthesis in the absence of GnRH. Castration also augmented the GnRH-stimu-lated release of LH and FSH from monolayer cultures 4.5-and 1.8-fold, respectively, and increased the amplitude of GnRH-stimulated LH and FSH pulses 5-and 2-fold in experiments with perifused pituitary cells. The EC60for GnRH was unaffected by castration. These data reveal that orchidectomy increases GnRH-inde-pendent FSH and LH secretion and also renders the pituitary more responsive to GnRH. Whereas changes in FSH secretion after orchidectomy are proportional to the increase in FSHβ mRNA, and the increase in basal LH secretion is proportional to the change in LHβ mRNA, the hypersecretion of LH after GnRH stimulation in vitro exceeds that of FSH because of increased LHβ mRNA, increased LH content, greater responsi-vess to GnRH, as well as possible specific translational and posttranslational changes. LH secretion is further augmented in vivo by increased pulsatile GnRH secretion. © 1990 by The Endocrine Society.