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SUMMARY
From the left adrenal of ten sheep foetuses and four lambs aged from 110 days after conception to 14 days after birth, adrenal venous blood was collected and assayed for cortisol, corticosterone and aldosterone. These steroids were secreted at all ages but the rate of secretion was greatly increased toward term and after birth. The increase coincided with morphological changes in the adrenal gland. At no stage was the rate significantly increased by corticotrophin, and in two young foetuses it was not decreased by dexamethasone. In two foetuses and one lamb, angiotensin II did not increase the rate of secretion of any of the three steroids significantly, and the blood pressure was raised only in the lamb. It is probable that the secretion of the steroids was maximal under the conditions of the experiments.
Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
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Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
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Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
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Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
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Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
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Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
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Previous studies of the GH–IGF system gene expression in growth plate using immunohistochemistry and in situ hybridization have yielded conflicting results. We therefore studied the spatial and temporal patterns of mRNA expression of the GH–IGF system in the rat proximal tibial growth plate quantitatively. Growth plates were microdissected into individual zones. RNA was extracted, reverse transcribed and analyzed by real-time PCR. In 1-week-old animals, IGF-I mRNA expression was minimal in growth plate compared with perichondrium, metaphyseal bone, muscle, and liver (70-, 130-, 215-, and 400-fold less). In contrast, IGF-II mRNA was expressed at higher levels than in bone and liver (65- and 2-fold). IGF-II expression was higher in the proliferative and resting zones compared with the hypertrophic zone (P < 0.001). GH receptor and type 1 and 2 IGF receptors were expressed throughout the growth plate. Expression of IGF-binding proteins (IGFBPs)-1 through -6 mRNA was low throughout the growth plate compared with perichondrium and bone. With increasing age (3-, 6-, 9-, and 12-week castrated rats), IGF-I mRNA levels increased in the proliferative zone (PZ) but remained at least tenfold lower than levels in perichondrium and bone. IGF-II mRNA decreased dramatically in PZ (780-fold; P < 0.001) whereas, type 2 IGF receptor and IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-4 increased significantly with age in growth plate and/or surrounding perichondrium and bone. These data suggest that IGF-I protein in the growth plate is not produced primarily by the chondrocytes themselves. Instead, it derives from surrounding perichondrium and bone. In addition, the decrease in growth velocity that occurs with age may be caused, in part, by decreasing expression of IGF-II and increasing expression of type 2 IGF receptor and multiple IGFBPs.
