Characterization and histologic localization of human growth hormone-variant gene expression in the placenta.

Abstract

The human growth hormone-variant (hGH-V) gene is one of five highly similar growth hormone-related genes clustered on the short arm of chromosome 17. Although the pattern of expression of the adjacent normal growth hormone (hGH-N) and chorionic somatomammotropin (hCS) genes in this cluster are well characterized, the expression of the hGH-V gene remains to be defined. In previous studies, we have demonstrated that the hGH-V gene is transcribed in the term placenta and expressed as two alternatively spliced mRNAs: one is predicted to encode a 22-kD hormone (hGH-V), the other retains intron 4 in its sequence resulting in the predicted synthesis of a novel 26-kD hGH-V-related protein (hGH-V2). In the present report, we document the expression of both of these hGH-V mRNA species in the villi of the term placenta, demonstrate an increase in their concentrations during gestation, and directly sublocalize hGH-V gene expression to the syncytiotrophoblastic epithelium of the term placenta by in situ cDNAmRNA histohybridization. The demonstrated similarity in the developmental and tissue-specific expression of the hGH-V gene with that of the related hCS gene suggests that these two genes may share common regulatory elements.

Placental Growth Hormone Levels in Normal Pregnancy and in Pregnancies with Intrauterine Growth Retardation

“…Placental GH is produced by the syncytiotrophoblast in vivo (8,9) and in vitro (lo), and we recently have demonstrated that this hormone is involved in autocrine mechanism in the syncytiotrophoblast (1 I).…”

DNase I-hypersensitive sites I and II of the human growth hormone locus control region are a major developmental activator of somatotrope gene expression

“…The hGH-N gene is expressed in the somatotrope and lactosomatotrope cells of the anterior pituitary, whereas the remaining four genes-hCS-L, hCS-A, hGH-V, and hCS-B-are expressed in the syncytiotrophoblastic layer of the placenta (5,6). hGH-N, hCS-A, and hCS-B are expressed at very high levels, constituting 2-3% of total mRNA in their respective tissues.…”

Placental growth hormone, pituitary growth hormone, insulin-like growth factor, and ghrelin in umbilical cord blood serum and amniotic fluid

“…The presence of this hormone in the syncytiotrophoblast was confirmed with immunohistochemical methods [6]. Besides, with molecular methods GH-V gene expression was shown in the placenta, and no expression of the GH-N gene, responsible for GH1 production, was demonstrated [7,11,12]. Moreover, the presence of PGH receptors was detected in the placenta, and this suggests a direct influence of PGH on placenta function through auto-and paracrine mechanisms, …”