Decreased ability of old male rats to secrete luteinizing hormone (LH) is not due to alterations in pituitary LH-releasing hormone receptors.

Abstract

The present study was undertaken to determine if the diminished release of LH in male rats with age in response to castration or LHRH injection is due to alternations in the number or affinity of LHRH receptors in the pituitary. Young (3-4 months old) and old (18-20 months) 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 less than 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 X 10(9) and 4.51 +/- 1.23 X 10(9) M1, 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 second experiment. Animals were castrated and given daily injections of testosterone propionate (500 micrograms/kg, im) for 13 days. Beginning on day 9, LHRH-a (250 micrograms/kg, sc) 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 X 10(9) M-1) or old (6.67 +/- 0.79 X 10(9) M-1) animals. In a third experiment, male rats were castrated and given injections of LHRH (166 ng/kg) at 30-min intervals for 4.5 h.(ABSTRACT TRUNCATED AT 400 WORDS)