We investigated whether chronic administration of LHRH to normal adult rats could increase the percentages of anterior pituitary gland (APG) cells that contain immunoreactive LH and/or FSH and gonadotropin secretion. Vehicle or 1 microgram LHRH was injected sc twice daily for 6 days, and rats were decapitated 16 h after the last injection. Treatment with LHRH caused nearly a doubling in the numerical density of LH and FSH cells and in the percentage of APG cells that contained LH or FSH. It also caused a shift in the gonadotroph population from LH and LH/FSH cells to LH/FSH cells. It did not change the mean size of gonadotrophs or APG weight. These changes at the light microscopic level were not accompanied by any apparent changes in LH cells at the ultrastructural level. However, they were accompanied by an approximate doubling of the basal serum LH and FSH concentrations, an increase in the APG FSH concentration, and an increase in the basal FSH release rate (measured in vitro). The results indicate that exogenous LHRH can be administered to increase numbers of gonadotrophs in the APG, synthesis of FSH in gonadotrophs, and basal serum LH and FSH concentrations.

We studied whether an increase in the basal LH release rate and/or the anterior pituitary gland (APG) LH response to LHRH is involved in maintaining normal or near-normal serum LH levels in monosodium L-glutamate (MSG)-treated rats which have small APGs for their body weight. Female rats were injected with MSG (4 mg/g BW) or saline on days 1, 3, 5, 7, and 9 after birth (day of birth = 0). At 8-9 weeks of age, saline-treated and MSG-treated rats were ovariectomized, and 7 days later, they were decapitated. Trunk blood was collected from 18 controls and 19 MSG-treated rats, and serum LH concentrations were measured by RIA. APGs were bisected and each hemi-APG was placed in culture medium for a 30-min preincubation period, followed by two 30-min incubation periods during which water or 10 or 30 ng LHRH were added to the medium. Despite the fact that the APGs of the MSG-treated rats were half the size of those of the saline-treated rats, the serum LH levels in the 2 groups were not different. Basal LH release rates (the response to water) and LHRH-induced LH release per mg APG were increased in MSG-treated rats. Calculation of the basal LH release rates and LHRH-induced LH release on the basis of the entire weights of the APGs showed no differences between the MSG-treated rats and the controls. In 6 additional control and 6 additional MSG-treated rats, the APG LH concentration was measured and was not different between the 2 groups. The results suggest that increases in both the basal LH release rate per mg APG and the amount of LH released per mg APG in response to LHRH are of importance in the maintenance of normal or near-normal serum LH concentrations in MSG-treated rats with small APGs.

We have correlated changes in rat anterior pituitary gland LH secretion with morphological changes in LH gonadotrophs as a function of time after ovariectomy. We decapitated rats on the early afternoon of proestrus or at 7, 19, 35, or 92 days after ovariectomy. Anterior pituitary gland LH concentration was determined in one-half of each anterior pituitary gland, and LH cells in the other half were stained immunocytochemically with rabbit anti-rat LHβ sera and examined at the ultrastructural level. In the proestrous rat, the shape of the basic LH cell was usually polygonal. The cells contained a single population of granules, usually scattered throughout a homogenous cytoplasm, and a nucleus which was generally ovoid. Golgi complexes were not commonly observed. Anterior pituitary gland LH secretion (synthesis and release) increased progressively as time after ovariectomy increased. Mean anterior pituitary gland LH concentration increased fivefold while serum LH concentration increased 22-fold by 92 days postovariectomy. At 7 and 19 days postovariectomy, the same basic LH cell was present except that the Golgi complexes became enlarged and prominent. In addition, another cell type, not commonly observed in proestrous rats, became more abundant. The cytoplasm of these cells was usually filled with small ovoid vesicles. The vesicles in these cells became larger and more irregular in outline by 35 days postovariectomy and a few signet ring cells were observed at this time. At 92 days postovariectomy, LH cells were nearly equally divided by cytoplasmic type into homogeneous, vesiculated, and signet ring. The cytoplasm surrounding the signet ring was homogeneous or vesiculated. As time after ovariectomy increased, the size of LH cells increased, secretion granules per LH cell profile increased, nuclei became more irregular in shape, and light-dense bodies became more obvious. In all LH cells we observed, the stain was only on the secretion granules and sometimes on the light-dense bodies. We did observe some vesiculated and signet ring cells which did not stain for LH. The results suggest that after ovariectomy in rats 1) an increase in LH concentration in individual cells and an increase in the release rate of LH from these cells is likely; 2) three cytoplasmic types of LH cells become prominent: homogeneous, vesiculated, and signet ring; 3) vesiculated cells arise from homogeneous cells and signet ring cells arise from either homogeneous or vesiculated cells; and 4) caution is warranted in the identification of LH gonadotrophs on the basis of morphological criteria alone.

A study was conducted to assess the importance of pituitary refractoriness to luteinizing hormone releasing hormone (LHRH) in ending the preovulatory surge of luteinizing hormone (LH) and in modulating the associated surge of follicle-stimulating hormone (FSH) in rat plasma. Phenobarbital-blocked proestrous rats were infused iv with LHRH at a constant rate of 50 ng/hr to restore the rising and plateau phases of the spontaneous surges of LH and FSH in plasma. Refractoriness to LHRH was demonstrated for LH but not FSH release when LHRH was infused beyond 2 hr. The plasma LH declined from high levels from 2 to 4.5 hr of infusion while the plasma FSH remained at an elevated plateau. The decline in plasma LH was not as rapid as that observed when the infusion was ended. Injection of a large dose (1 μg) of LHRH at 2 or 3.5 hr after the start of infusion caused substantial increases in plasma LH and FSH but only the LH response after the later injection was less than that observed in other rats given the injection earlier. The results suggest that pituitary refractoriness to LHRH plays a minor role in expediting the decline in the plasma LH during the latter portion of the LH surge and that it has no appreciable effect on the pattern of the plasma FSH at this time.

Changes in rat anterior pituitary gland LH secretion were correlated with changes in morphology of pituitary LH cells during a simulated preovulatory surge of LH in serum. In phenobarbital blocked proestrous rats, LHRH was infused i.v. at a constant rate (50 ng/h) previously shown to restore the LH surge. Rats were decapitated prior to or after the start of LHRH infusion. Pars distalis tissue was stained with anti-rat LHβ sera and examined by electron microscopy.