Maternal Modulation of Growth Hormone Secretion in the Neonatal Rat. I. Involvement of Milk Factors*

Abstract

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.

Role of Hypothalamic Factors (Growth-Hormone-Releasing Hormone and Gamma-Aminobutyric Acid) in the Regulation of Growth Hormone Secretion in the Neonatal and Adult Rat

“…In agreement with the finding of Wehrenberg [32], administration of GRH antibody diminished the plasma GH levels of 2-day-old rats in a dose-related fashion (fig. 2); this decrease could be due to the binding of either the endogenous GRH or of the milk-borne GRH [19,33]. The ab sence of a GH-releasing effect of exogenous GRH on day 2 of life is in agreement with the findings of other authors [10,12,19].…”

“…2); this decrease could be due to the binding of either the endogenous GRH or of the milk-borne GRH [19,33]. The ab sence of a GH-releasing effect of exogenous GRH on day 2 of life is in agreement with the findings of other authors [10,12,19]. The decrease in plasma GH after immunoneutralization, indicating a stimulatory effect of the endogenous GRH, is in apparent contradiction with the finding that there is no increase after exogenous GRH.…”

“…Immunoreactive GRH has been detected in the rat hypothalamus in the late prenatal period and immediately after birth [II,17,18], and pituitary GH secretion of the new born rat is stimulated by GRH in vitro [3,4,9,29]. Adminis tration of anti-GRH serum significantly decreased serum GH concentrations on the 21st fetal day and on postnatal days 1-20 [15, 18, 32], but since GRH was detected in placenta [5] and in milk [19,33] passive immunization could affect both endoge nous or maternal GRH.Received: November 2, 1989 Accepted after revision: February 9, 1990 To test if GH secretion in the newborn rat is under the con trol of the hypothalamus via GRH or GABA, we tried to find a stimulus inducing the release of hypothalamic factors. N-methyi aspartic acid (NMA) is known to elicit GH secretion in the adult rat [21] and our present data indicate that stimulation of release of a hypothalamic factor from the arcuate nucleus (prob ably GRH) was involved in the effect of NMA.…”

Role of Serum Myostatin during the Lactation Period

“…In addition, it has been also shown that recombinant human growth hormone (GH) inhibits myostatin mRNA and protein expression in cultured myogenic cells, and long term administration of GH to GH-deficient patients reduced myostatin mRNA expression in skeletal muscle [34,35]. It is thought that GH is a major regulatory factor of growth in neonatal animals and that the plasma GH levels of rats are high during the neonatal period and then decline with advancing age [36][37][38]. Furthermore, some reports have shown that the basal level of plasma glucocorticoid increases with advancing age [39,40].…”

Early weaning impairs body composition in male mice

“…One of these compounds is a growthhormone-releasing hormone, which is found in both human and mice milk (Kacsoh et al, 1990) and can stimulate growth hormone (GH) secretion from the pituitary of neonates both in vitro and in vivo (Kacsoh et al, 1989). In addition, many of the GH's growth promoting effects are mediated by insulin-like growth factor-1 (Gomes et al, 2003;Tirapegui, 1999;Tirapegui, Baldi, Ribeiro, 1996), which is also found in maternal milk (Baxter, Zaltsman, Turtle, 1984).…”