Anna E. Miller

Aging effects on hypothalamic dopamine and norepinephrine content in the male rat.

Hypothalamic content of dopamine and norepinephrine was measured in young (4 mo) and aged (24-26 mo) male rats by aluminum oxide adsorption and microfluorescence. Hypothalamic content of both dopamine and norepinephrine was significantly less in aged than in the young groups. Average dopamine content of the young and aged groups was 32.5 +/- 9.3 and 15.6 +/- 2.5 ng/hypothalamus, respectively. Norepinephrine content averaged 47.6 +/- 10.7 and 22.8 +/- 1.8 ng/hypothalamus in the young and aged groups. These data suggested that alterations in hypothalamic catecholamine function contribute to changes in endocrine control mechanisms during aging.

Serum LH Levels Following Multiple LHRH Injections in Aging Rats

Summary The effect of three serial injections of 500 ng of LHRH on serum LH was tested in young (4-5 mo) and aged (24-28 mo) male and female Long-Evans rats. Aged female groups were rats showing constant estrous or pseudopregnant vaginal cytology (at least 10 days of cornified or leucocytic vaginal smears, respectively) which were compared to young female rats at estrous and diestrous stages of their ovarian cycle. The increase in serum LH following the first LHRH stimulation was less in the aged than in the young groups. Serum LH concentrations in the aged female group were progressively increased following the second and third LHRH injections. The increase in serum LH following the second and third LHRH injections was similar in young and aged female groups. LH concentration in blood samples collected before LHRH injection was progressively increased in both aged female groups. Although LH was greater in young than aged males after the first LHRH injection, LH concentrations after the second and third injections were similar in both ages. These results indicate that aged rat pituitaries can sustain higher serum LH concentrations than are normally found in their circulation and suggest that failure of hypothalamic hormonal stimulation of LH release contributes to the loss of reproductive function in aging. The increase in LH following multiple LHRH injections in aged female rats reflects increased pituitary responsiveness following the priming effect of the first stimulation and reduced LH clearance.

Hypothalamic LH-releasing activity in young and aged intact and gonadectomized rats

Hypothalamic LH-releasing activity content was measured in young (3-5 mo) and aged (22-26 mo) intact and gonadectomized male and female rats. Hypothalamic extracts (0.25, 0.5 and 1.0 hypothalamus equivalents) from young and aged rats were incubated with untreated hemisectioned rat pituitaries in medium 199. All hypothalamic extract treatments stimulated LH release from the incubated pituitaries. Increased amounts of hypothalamic extracts added to to the incubation medium proportionally increased LH release. There were no differences in LH release stimulated by young or aged hypothalamic extracts from either the intact or gonadectomized groups. In addition serum testosterone concentrations were reduced in the aged male rats and serum LH was lower in aged male and female rats than in the young groups. Although serum LH was increased after gonadectomy in all groups, the increase was of smaller magnitude in the aged rats. These data indicate significant alterations in the responsiveness of the hypothalamus to steroid feedback in the aged rat. Although the hypothalamus contains sufficient LH-releasing activity to stimulate higher levels of pituitary and gonadal endocrine function, aging effects on the neuroendocrine control mechanisms inhibit hypothalamic hormone function.

AGE EFFECTS ON THE HYPOTHALAMIC-PITUITARY-GONADAL CONTROL SYSTEM IN THE RAT

Early recognition that hormones were major regulators of body function has made studies of aging on endocrine control mechanisms attractive to gerontologists. Age alterations in reproductive control systems are well documented. A better understanding of aging changes in the reproductive control system of both man and other species should not only aid in the identification of appropriate animal models to use in the study of aging effects on human physiological systems, but also allow development of clinical procedures which could restore certain endocrine functions and improve the quality of life with advancing age.