Ontogeny of growth hormone receptors in human tissues: an immunohistochemical study

Both experimental and clinical studies suggest that human GH (hGH) may have a functional role during early stages in human development. To determine when receptors for hGH appear in specific target cells, we carried out an immunohistochemical analysis of six tissues obtained from 20 fetuses (8.5-20 weeks fetal age [FA]), two term infants, one 11-yr-old male, and one 43-yr-old male. Liver parenchymal and bile duct cells showed specific staining from the earliest FA examined (8.5 weeks); in fetal liver, the intensity of the immunoreaction was greatest in hepatocytes surrounding the central veins and portal triads, whereas the numerous hematopoietic cells exhibited little to no immunostaining. Kidney tissues also showed positive localization at 8.5-9 weeks FA. By 13 weeks, epithelial cells of most tubules were immunoreactive, with medullary tubules showing stronger staining than those in the cortex, whereas visceral epithelial cells of glomeruli were weakly positive; metanephrogenic blastemal cells were negative. A similar immunostaining pattern was observed in midgestation and postnatal kidneys, except that glomerular staining was lost by 19 weeks FA. Fetal zone cells of fetal adrenals showed weak immunostaining beginning at 13-14 weeks; glomerulosa cells stained intensely in the postnatal adrenal. Epithelial crypt cells in both small and large intestine immunostained beginning at 19-20 weeks; a similar pattern was observed in postnatal sections. Dermal fibroblasts and skeletal muscle of abdominal skin were positive from 8.5 weeks. Epidermal cells first showed immunostaining at 13-14 weeks; germinal layer cells showed the most intense reaction until 19-20 weeks, when the staining pattern became uneven throughout the epidermal layers. Epithelial cells in hair follicles and sebaceous glands were positive from 13-14 weeks; by 19-20 weeks, these cells were the most intensely immunostained in skin sections. Lung tissue was negative from 8.5-20 weeks, as well as postnatally. Vascular endothelial and smooth muscle cells routinely stained from 8.5 weeks FA in all tissues examined. We conclude that immunoreactive hGH receptors can be identified in early fetal, as well as postnatal, tissues and that the pattern of cellular immunostaining develops gradually throughout gestation in a very tissue-specific manner.