GROWTH HORMONE-RELEASING HORMONE (GHRH)-GH-SOMATIC GROWTH AND LUTEINIZING-HORMONE (LH)RH-LH-OVARIAN AXES IN ADULT FEMALE TRANSGENIC MICE EXPRESSING HUMAN GH GENE

We have examined alterations in the hypothalamo-pituitary GH-somatic g rowth axis and the hypothalamo-pituitary LH-ovarian axis in a line of transgenic ICR mice expressing human GH (hGH) under the influence of t he whey acid protein promoter. Transgenic female mice weighed twice as much as control females and were infertile. The size of the anterior pituitary (AP) was 1/3 that of the controls. In transgenic mice, acina r cells in the mammary and mandibular glands displayed hGH-immunoreact ivity, and plasma hGH was detected by radioimmunoassay. In the medial basal hypothalamus (MBH) of transgenic females, the immunoreactive-GHR H level was decreased (P<0.01). There was a corresponding reduction in the number of GHRH-immunoreactive neurons in the arcuate nucleus (ARC ) and in the immunostaining of GHRH nerve terminals in the median emin ence. The level of somatostatin (SRIH) in the MBH was increased (P < 0 .05), and SRIH-immunoreactive neurons in the periventricular nucleus ( PeV) were increased in size and number in transgenic mice. The MBH lev el of LHRH in transgenic animals was greater (P<0.01) than in controls , although there was no apparent difference in the number of LHRH-immu noreactive neurons or in LHRH level in the preoptic area. There are fe wer SRIH- and LHRH-immunoreactive neurons in the ARC in transgenic mic e. Cells in the AP for GH, PRL, and LH were fewer in transgenic mice. The ovary suffered disturbance of follicular development and of corpor a lutea formation. These results demonstrate that chronic overproducti on of hGH may profoundly affect the organization of the GHRH/SRIH-GH-s omatic growth axis and the LHRH-LH-ovarian axis due to reduction of GH RH-, SRIH- and LHRH-neurons in the ARC and increase of SRIH-neurons in the PeV.