Severe uremia depresses the ability of perifused rat pituitary cells to secrete growth hormone in response to growth hormone releasing hormone.

Abstract

To examine whether growth hormone (GH) secretion is impaired by chronic renal failure (CRF) and to gain some insight into the influence of uremia itself and associated malnutrition, the GH secretory response of dispersed anterior pituitary cells perifused with GH-releasing hormone (GHRH) was investigated in 5/6 nephrectomized (UREM, N = 15) and three groups (N = 15 each) of normal renal function, sham-operated rats under three different nutritional conditions: fed "ad libitum" (SAL), pair-fed with a diet similar to the UREM group (SPF), and pair-fed with a diet similar to the UREM group in terms of protein ingestion but calorically supplemented up to intake of SAL group (SPF+). Ten days after 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, respectively), 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 secretory rate (ng/min/10(7) cells) in the four groups. A fixed sequence of progressively increasing GHRH doses resulted in a lower overall mean GH secretion in UREM rats (15.8 +/- 1.6 ng/min/10(7) cells), as compared 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+ (49.4 +/- 5.1 ng/min/10(7) cells, P < 0.01) groups. Analysis of dose-response curves showed that the maximal secretory response was produced by the same concentration of GHRH (10 nM) in the four groups and was lower (P < 0.01) in UREM 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 the half of maximal effect was identical, close to 1 nM, in the four groups of animals. This study provides direct evidence that the ability of pituitary cells to secrete GH in response to GHRH is depressed in severe CRF. The lower secretory capacity of pituitary gland is only partly dependent on caloric malnutrition associated with CRF. Data of dose-response curves suggest that decreased GH secretion may be related to a lesser number of pituitary receptors for GHRH.