Maternal modulation of growth hormone secretion in the neonatal rat. I. Involvement of milk factors.

The present experiments investigated the time course of maternal modulation of GH secretion and examined the possible role of milk in the regulation of GH secretion in neonatal rats. Serum GH concentrations in neonatal rats were high at birth and declined over time postpartum. Separation of rat pups from their mothers decreased, while a subsequent period of suckling increased, serum GH levels in rat pups on postpartum days 1-14, but not on day 20. The water-soluble fraction (infranatant) of rat milk contained immunoreactive (ir) rat GH-releasing hormone (rGHRH)-like material (725.06 +/- 81.29 pg/ml), ir-somatostatin-like activity (1.64 +/- 0.2 ng/ml), and irGH (4.79 +/- 0.73 ng/ml). The concentrations of these hormones tended to decrease with time postpartum and were positively correlated with each other (r = 0.70; P less than or equal to 0.0001). IrPRL was also present in the infranatant (148.44 +/- 14.55 ng/ml), but levels were not correlated with the other hormones detected. Milk infranatant stimulated GH secretion from perifused neonatal rat pituitary glands in vitro. Milk infranatant also stimulated GH secretion in vivo when administered sc or intragastrically to 2- or 8-day-old rat pups. The GH-releasing effect was not due to gastric distension or nonspecific nutritive components, as neither 0.9% saline nor nutrients (5% glucose and 10% BSA) increased serum GH levels. The presence of high concentrations of irGHRH in rat milk infranatant and the strong correlation between the irGHRH concentrations of milk samples and the in vitro GH response (r = 0.71; P less than or equal to 0.005) suggested that this peptide is a major candidate for producing the in vitro and in vivo GH-stimulating activity in rat milk. However, the minimally effective concentration of synthetic rGHRH required to stimulate GH release in the superfusion system was between 1-10 nM, which exceeds milk irGHRH levels by 100- to 1000-fold. Moreover, in vivo administration of synthetic rGHRH (sc or intragastrically) was unable to increase serum GH concentrations in 2-day-old pups, although a large dose (100 ng/g) of human GHRH sc was effective. These findings indicate that rat milk may be an important maternal factor that modulates GH secretion and, consequently, growth during the neonatal period. Rat milk has GH-releasing activity both in vivo and in vitro in neonatal rats, but the GH-releasing activities of milk are probably only minimally due to its rGHRH content.