Interaction of Growth Hormone-Releasing Hormone with the Insulin-Like Growth Factors During Prenatal Development in the Rat^*

Abstract

The placenta is a chimeric organ that produces all the components of the hypothalamic-pituitary GH axis. We propose that placental GH-releasing hormone (GHRH) stimulates placental GH-like hormones which in turn stimulate production of the insulin-like growth factors (IGFs), IGF-I and IGF-II, and these placental IGFs are important for growth and development of the placenta as well as the fetus. To test this hypothesis, pregnant rats were given either GHRH antisera or preimmune sera ip from days 7-19 of gestation. Fetuses were killed on day 19, and IGF-I and IGF-II tissue and serum concentrations in the mother and fetus were measured by RIA. IGF-II receptor content was measured by Western analysis. IGF-I and IGF-II messenger (m) RNA levels were measured in the placentas as well as in the fetal livers. The GHRH antibody titer was highest at day 19 of gestation but continued to be present through day 20 of postnatal development. Although placental weights did not differ, antibody-treated animals had higher placental IGF-I and IGF-II levels (I, 108 +/- 6 (SD); II, 126 +/- 5 ng/g, respectively) vs. control animals (I, 88 +/- 2.5 (SD); II, 48 +/- 11 ng/g) in pooled specimens. The IGF-II receptor was also up-regulated in placentas from antibody-treated mothers. The fetuses of antibody-treated (A) mothers were larger than the controls (C) (A, 2.615 g; C, 2.49 g, P less than 0.05). Levels of both IGFs were significantly increased in livers of antibody treated fetuses (IGF-I: A, 15 +/- 1 (SD); C, 12 +/- 0.8 ng/g; and IGF-II: A, 295 +/- 10 (SD); C, 233 +/- 10 (SD) ng/g). In addition, the concentration of the IGF-II receptor in liver of antibody-treated fetuses was also increased. Further, pooled fetal sera from antibody-treated fetuses had higher levels of IGF-II than controls (A, 950 ng/ml; C, 700 ng/ml), and the circulating IGF-II receptor was increased as measured by Western analysis. In the liver, IGF-II mRNA levels of antibody-treated fetuses were increased to 117% of controls, whereas IGF-I mRNA levels were undetectable. The placenta showed no increase in placental lactogen or GH mRNA, whereas IGF-II and GHRH mRNA were slightly increased in antibody-treated animals. In conclusion, these data suggest that GHRH may interact with the IGFs in a different fashion during prenatal development then during postnatal development.(ABSTRACT TRUNCATED AT 400 WORDS)

Developmental changes in the expression of growth hormone‐releasing hormone and pituitary adenylate cyclase‐activating polypeptide in zebrafish

“…Therefore, the placenta could represent the early source of GHRH and PACAP in mammalian vertebrates. In support of this hypothesis, placental GHRH has been isolated at embryonic day 7 in the rat and is thought to regulate maternal production of insulin-like growth factor-II (IGF-II; Spatola et al, 1991).…”

“…GHRH and its receptor are first expressed in the rat at embryonic day (E) 16 -18, when fetal pituitary somatotrophs differentiate and growth hormone transcripts appear (Ishikawa et al, 1986;Lin et al, 1992). However, placental ghrh mRNA was detected as early as E7 in the rat and is thought to regulate fetal growth maternally (Spatola et al, 1991). In the chick, GHRH was found to enhance corticosterone-stimulated somatotroph differentiation (Dean et al, 1999), and GHRH stimulated GH release from differentiated somatotroph cells (Porter et al, 1995).…”

Identification and Characterization of a Receptor from Goldfish Specific for a Teleost Growth Hormone-Releasing Hormone-Like Peptide

“…In fact, GHRH was also found to regulate sleep [21, 22], gonadal [23, 24, 25, 26], immune [20] and placental functions [27]. Furthermore, GHRH was implicated in the regulation of fetal GH secretion during the embryonic period [28, 29]. …”

Presence of a Bioactive and Immunoreactive Growth-Hormone-Releasing-Factor-Like Substance in Porcine Placenta

“…This might explain why decapitated swine fetuses can maintain a relatively nor-mal growth rate in útero [22,23]. Yet the pos sibility still remains that placental GRF may be secreted into the fetal circulation and pro vide extrahypothalamic stimulatory input to the fetal pituitary gland [7], It has been found that intraperitoneal administration of GRF antiserum to pregnant rats results in an upregulation of IGF-I and 1GF-II and of the IGF-II receptor in placenta and fetus, thereby sub stantiating the involvement of the placenta in the in útero regulation of the secretion of somatotropic hormones [24], It was also re ported that the stage of gestation had no effect on GRF concentration in the rat placenta, although total contents of GRF increased pro gressively in relation to placental growth [7], Similarly, the total content of immunoreactive GRF per placenta increased from days 50 to 100 of gestation in sheep [9]. On the other hand, the concentrations were higher in late gestation (days 100-140) than in early gesta tion (days 50-80) [9], Such a difference could not be detected in the present trials, since pla cental extracts were only obtained during late gestation.…”