Submission Number: CHA-4-20-2

Abstract Number: 247

NEUROENDOCRINE FUNCTION IN FEMALE TRANSGENIC MICE EXPRESSING THE HUMAN GROWTH HORMONE-RELEASING HORMONE GENE.

V Chandrashekar* and A Bartke*

Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62901-6512 ¹

Abstract:
A number of studies have shown that GH influences growth and metabolism, but its role in the control of neuroendocrine function is poorly understood. Pituitaries of mice expressing the hGHRH gene secrete excess GH and these transgenic mice are ideal experimental model to assess the role of homologous GH in hypothalamic-pituitary function. Therefore, young adult female mice expressing the hGHRH gene with mouse metallothionein-I promoter and their normal siblings were ovariectomized. On day 8 after ovariectomy, two experiments (N=7-12 mice/subgroup) were conducted. In experiment I, mice were primed (sc injections) with 0.5 g estradiol benzoate (EB) in oil and 24 h later injected with 5 g EB/100 g BW. The next day, these mice were injected (ip) with either saline or GnRH (1 ng/g BW), and 15 min later blood was obtained via heart puncture. In experiment II, ovariectomized mice were injected either with oil or were primed with 0.5 g EB and 24 h later treated with 10 g EB/100 g BW in oil. On the next day, blood was obtained as in experiment I. Plasma IGF-I, LH and, PRL levels were determined by RIAs. As expected, the circulating IGF-I levels were increased (P<0.001) in transgenic mice. Administration of GnRH increased (P<0.001) plasma LH levels in both transgenic and normal mice. However, this LH response was significantly (P<0.001) attenuated in mice expressing the hGHRH gene. The plasma LH response to ovariectomy was reduced (P<0.001) in transgenic mice relative to normal siblings. However, the suppressive effect of EB on LH secretion was similar in both groups of mice. The basal plasma PRL levels were similar in oil-injected, ovariectomized transgenic mice and normal siblings. Administration of EB increased (P<0.001) plasma PRL concentrations in transgenic and normal mice. However, this estrogen effect on plasma PRL levels was decreased (P<0.01) in mice secreting excess IGF-I. These data suggest that excess endogenous GH/IGF-I secretion can influence GnRH action on LH secretion and modify the estrogen effect on PRL secretion in mice (Supported by NIH Grant RR15012).

Keywords: Pituitary function, Estrogen effects

This abstract is being presented at: 2:15 PM in session:
SESSION 12: NEUROENDOCRINOLOGY I