PARENT SESSION

(W657) PITUITARY FUNCTION IN YOUNG AND AGING FEMALE GROWTH HORMONE RECEPTOR GENE DISRUPTED MICE.

Chandrashekar, Varadaraj¹, Abaonza, Kristin¹, Chinwokwu, Olatubosun¹, Bartke, Andrzej^{1, 2}, ¹ Southern Illinois University School of Medicine, Department of Physiology, Carbondale, IL² Southern Illinois University School of Medicine, Internal Medicine, Springfield, IL

ABSTRACT- A number of recent findings have demonstrated that insulin-like growth factor-I (IGF-I) plays an important role in longevity and it influences gonadal function. Growth hormone receptor gene knockout (GHR-KO) mice are IGF-I-deficient and they live longer than their normal siblings. However, the pituitary function in aging female GHR-KO mice is not known. To evaluate this, young (4 months of age) and two aging groups (12 and 19-22 months of age) of female GHR-KO mice and their normal female siblings were gonadectomized. On day 8 after ovariectomy, mice were primed (sc injection) with 0.5 g estradiol benzoate (EB) in oil and 24 h later, to decrease the LH secretion before stimulating the pituitary with GnRH, all mice were injected with 5 g EB/100 g BW. Next day, these mice were injected (ip) with either saline or GnRH (1 ng/g BW) in saline (N=6-12 mice/group), and 15 min later blood was obtained via heart puncture. Plasma LH and PRL levels were determined by RIAs. The basal plasma LH levels were similar in GHR-KO and in normal mice of various age groups. GnRH treatment increased (P<0.001) plasma LH concentrations in all groups of animals. However, this plasma LH response was decreased in aging normal siblings relative to normal young mice (12 months of age: P<0.005; 19-22 months of age: P<0.01). In comparison with young and aging normal mice, the LH response to GnRH treatment was attenuated (P<0.001) in both young and aging GHR-KO mice. The increases in plasma LH levels in response to GnRH treatment in aging GHR-KO mice were similar relative to similarly treated young GHR-KO mice. Although the plasma PRL responses to estrogen treatment were similar in young and old normal siblings, these responses were reduced in both groups of aging GHR-KO mice (12 months of age: P<0.005; 19-22 months of age: P<0.025) relative to young GHR-KO mice. These results indicate that normal secretion of IGF-I is required for the full effect of GnRH on LH secretion and the already attenuated GnRH effect in young GHR-KO mice is not further affected by aging. Furthermore, disruption of IGF-I secretion affects the estrogen action on PRL secretion in aging mice. Thus IGF-I plays a role in the control of the pituitary function. However, it is not known whether these alterations contribute to the longevity in GHR-KO mice (Supported by NIH Grants HD-37950 and AG-19899).

KEY WORDS: insulin-like growth factor-I, Aging, LH, Prolactin