Altered pituitary growth hormone (GH) regulation in streptozotocin-diabetic rats: a combined defect of hypothalamic somatostatin and GH-releasing factor.

Diabetes mellitus in the rat is associated with loss of pulsatile GH secretion. An interplay between hypothalamic GH-releasing factor (GRF) and inhibitory factor [somatostatin (SRIF)] secretion is thought to account for episodic pituitary GH release. An increase in SRIF tone/action or a decrease in GRF release/response in diabetic rats could account for the suppressed GH levels. Pituitaries from streptozotocindiabetic rats contained less GH than controls (15.9 ± 2.5 us. 29.5 ± 4.6 μ/mg; P < 0.05) despite normal somatotrope representation, as demonstrated using immunofluorescence studies. Basal GH secretion from monolayer culture of dispersed anterior pituitary (AP) cells from diabetic rats was proportionately decreased (150 ± 10 us. 103 ± 10 ng/105 cells; P < 0.005). GRF (10-11.10-8 M)-induced release of GH from AP cells was decreased in diabetic rats (maximum response to 10-8 M GRF, 401 ± 60 us. 618 ± 41 ng/105 cells; P < 0.01); however, sensitivity to GRF was unchanged (EC50,79 ± 41 us. 128 ± 67 pM). By...