SEVERE UREMIA DEPRESSES THE ABILITY OF PERIFUSED RAT PITUITARY-CELLS TO SECRETE GROWTH-HORMONE IN RESPONSE TO GROWTH-HORMONE RELEASING HORMONE

To examine whether growth hormone (GH) secretion is impaired by chroni c renal failure (CRF) and to gain some insight into the influence of u remia itself and associated malnutrition, the GH secretory response of dispersed anterior pituitary cells perifused with GH-releasing hormon e (GHRH) was investigated in 5/6 nephrectomized (UREM, N = 15) and thr ee groups (N = 15 each) of normal renal function, sham-operated rats u nder three different nutritional conditions: fed ''ad libitum'' (SAL), pair-fed with a diet similar to the UREM group (SPF), and pair-fed wi th a diet similar to the UREM group in terms of protein ingestion but calorically supplemented up to intake of SAL group (SPF+). Ten days af ter nephrectomy, UREM rats had severe CRF, as shown by much higher (P < 0.0001) serum urea nitrogen concentrations (X +/- mean +/- SE) than sham groups (59 +/- 6 versus 8 +/- 0, 9 +/- 0, and 5 +/- 0 mmol/L, res pectively), and they were growth retarded, as shown by lower gains (P < 0.0001) in weight (13.5 +/- 2.5 versus 62 +/- 2.1, 20.5 +/- 1.9, and 50.4 +/- 1.0 g) and length (2.9 +/- 0.2 versus 5.8 +/- 0.1, 3.6 +/- 0 .1, and 5.6 +/- 0.1 cm). Perifusion studies showed similar basal GH se cretory rate (ng/min/10(7) cells) in the four groups. A fixed sequence of progressively increasing GHRH doses resulted in a lower overall me an GH secretion in UREM rats (15.8 +/- 1.6 ng/min/10(7) cells), as com pared with SAL (50.8 +/- 9.0 ng/min/10(7) cells, P < 0.01), SPF (33.0 +/- 3.3 ng/min/10(7) cells, P < 0.05), and SPF+ (49.1 +/- 5.1 ng/min/1 0(7) cells, P < 0.01) groups. Analysis of dose-response curves showed that the maximal secretory response was produced by the same concentra tion of GHRH (10 nM) in the four groups and was lower (P < 0.01) in UR EM than SAL and SPF+ rats (34.9 +/- 5.0 versus 115.7 +/- 28.4 and 98.9 +/- 9.8 ng/min/10(7) cells). The concentration of GHRH that caused th e half of maximal effect was identical, close to 1 nM, in the four gro ups of animals. This study provides direct evidence that the ability o f pituitary cells to secrete GH in response to GHRH is depressed in se vere CRF. The lower secretory capacity of pituitary gland is only part ly dependent on caloric malnutrition associated with CRF. Data of dose -response curves suggest that decreased GPI secretion may be related t o a lesser number of pituitary receptors for GHRH.