Pituitary and hypothalamic glucose-6-phosphate dehydrogenase: effects of estradiol and age in C57BL/6J mice.

Activities of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6-PGDH) were measured in the mediobasal hypothalamus and pituitary gland of C57BL/6J mice throughout their lifespan. Activities of pituitary G6PDH, pituitary 6-PGDH, and hypothalamic G6PDH increase with age in female mice, assayed 7 days after ovariectomy, but not in intact females or males. Pituitary G6PDH specific activity is increased by middle-age (13-14 months) in females, before the onset of acyclicity, and remains elevated throughout the acyclic phases of persistent vaginal cornification and persistent diestrus. This increase in activity is ovary dependent, because it can be prevented by long term (12-month) ovariectomy. The increased activity is not linked to pituitary tumorigenesis and does not result from trapped blood cells, as evaluated by studies with 51Cr-labeled erythrocytes. Responses to physiological levels of estradiol (E2) were analyzed with a graded series of chronic polyethylene implants or after a single sc injection in ovariectomized mice aged 5-22 months. The responsiveness of pituitary G6PDH to E2 is not altered during aging. Young cycling (6 months old) and older acyclic mice (19 months old) displaying persistent vaginal cornification show equivalent increases of about 100% in G6PDH specific activity after chronic E2 treatment and similar time courses of induction after a single E2 injection. Pituitary G6PDH is maximally induced (30% increase) by 48 h after E2 injection in all age groups. In addition, the rates of decline in pituitary G6PDH specific activity after ovariectomy are similar in young and older mice (half-life, 4 days). The specific activity of G6PDH in the mediobasal hypothalamus and blood is unaffected by E2 administration. The relatively low doses of E2 used here fail to alter 6-PGDH specific activity in pituitary or brain. These findings indicate that female reproductive senescence in mice is not associated with generalized losses of sensitivity and responsivity to E2 throughout the neuroendocrine axis.