Decreased Ability of Old Male Rats to Secrete Luteinizing Hormone (LH) Is Not due to Alterations in Pituitary LH-Releasing Hormone Receptors*

Abstract
It was determined if the diminished release of LH [luteinizing hormone] in male rats with age in response to castration or LHRH injection is due to alterations in the number or affinity of LHRH receptors in the pituitary. Young (3-4 mo. old) and old (18-20 mo. old) male Sprague-Dawley rats were killed 0, 2, 4 and 8 days after castration. Serum was collected for determination of LH concentrations, and anterior pituitaries were removed for analysis of LHRH receptors. The numbers and affinity constants of receptors were determined by Scatchard analysis using iodinated des-Gly10-[D-Ala6]LHRH ethylamide (LHRH-a) as ligand. Plasma LH in young rats increased from 54 ng/ml in intact animals to 319 ng/ml 8 days after castration, but in old animals, LH increased only from 47 to 119 ng/ml during the same period (P < 0.01). However, there were no age-related differences in LHRH receptors in intact animals, and both young and old animals showed similar increases in pituitary LHRH receptors after castration when expressed either as receptors per pituitary (young, 132 .+-. 27 to 262 .+-. 43 fmol/pituitary; old, 175 .+-. 27 to 299 .+-. 19 fmol/pituitary) or as receptors per mg protein (young, 420 .+-. 48 to 847 .+-. 172 fmol/mg protein; old, 432 .+-. 38 to 866 .+-. 62 fmol/mg protein). Receptor affinity was not statistically different in intact young or old animals (4.51 .+-. 0.41 .times. 109 and 4.51 .+-. 1.23 .times. 109 M-1, respectively), and receptor affinity increased in both groups in response to castration. The capacity of young and old male rats to produce LHRH receptors in response to exogenous LHRH was tested in a 2nd experiment. Animals were castrated and given daily injections of testosterone propionate (500 .mu.g/kg i.m.) for 13 days. Beginning on day 9, LHRH-a (250 .mu.g/kg, s.c.) was injected for 5 days. The rises in serum LH after a single injection of LHRH-a were similar in young and old animals on the first and fifth days of LHRH-a treatment. LHRH receptors at the cessation of hormone therapy also increased similarly in both young and old animals in response to LHRH-a (715 .+-. 135 and 811 .+-. 203 fmol/mg protein, respectively). Receptor affinity was not statistically different in young (6.27 .+-. 0.40 .times. 109 M-1) or old (6.67 .+-. 0.79 .times. 109 M-1) animals. In a 3rd experiment, male rats were castrated and given injections of LHRH (166 ng/kg) at 30-min intervals for 4.5 h. The initial injections of LHRH produced similar increases in plasma LH in both young and old animals, but continued injections increased LH levels more in young than in old animals. Apparently there are no significant differences in the basal number or affinity of LHRH receptors between young and old male rats and LHRH receptors increase similarly in the 2 groups in response to LHRH-a; after castration, sufficient LHRH is released from the hypothalamus to stimulate LHRH receptor formation to a similar degree in both young and old male rats; and deficiencies in LH release develop in response to repeated injections of LHRH in old male rats that appear to be related to postreceptor changes within the gonadotrope.