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Whether growth hormone stimulates longitudinal bone growth by a direct effect at the site of the growth plate or indirectly by increasing the concentration of circulating somatomedins (insulin-like growth factors) has been the subject of controversy. Immunohistochemical methods were used to explore the localization and distribution of insulin-like growth factor I (IGF-I) immunoreactivity in the epiphyseal growth plate of the proximal tibia of male rats. Cells in the proliferative zone of the growth plate of normal rats exhibited a bright immunofluorescence, whereas cells in the germinal and hypertrophic zones stained only weakly. In rats subjected to hypophysectomy, the number of fluorescent cells was markedly reduced. When the hypophysectomized rats were treated with growth hormone, either systemically or at the site of the growth plate, the number of IGF-I-immunoreactive cells in the proliferative zone was increased. The results show that IGF-I is produced in proliferative chondrocytes in the growth plate and that the number of IGF-I-containing cells is directly regulated by growth hormone. These findings suggest that IGF-I has a specific role in the clonal expansion of differentiated chondrocytes and exerts its function locally through autocrine or paracrine mechanisms.

Many lines of evidence indicate that the activity of sebaceous glands can be modulated by neuropeptides. Direct evidence in man, however, is still missing. We show that SZ95 sebocytes, an immortalized human sebaceous gland cell line, express receptors for alpha-melanocyte-stimulating hormone. Reverse transcription polymerase chain reaction with primers against the five melanocortin receptors and immunofluorescence studies using an antibody directed against a peptide corresponding to the amino acids 2-18 of the human melanocortin-1 receptor disclosed specific transcripts and immunoreactivity for melanocortin-1 receptor in these cells. Melanocortin-1 receptor expression was confirmed in sebocytes of normal human skin by immunohistochemistry. In contrast, no immunostaining for the melanocortin-5 receptor could be detected in sebocytes in situ, in accordance with the lack of specific transcripts for this melanocortin receptor in SZ95 sebocytes. As cytokines play an important role in the recruitment of inflammatory cells in acne and related disorders and alpha-melanocyte-stimulating hormone exerts immunomodulatory effects in many other cell types, we investigated the effect of alpha-melanocyte-stimulating hormone on interleukin-8 secretion by SZ95 sebocytes. Treatment with interleukin-1beta resulted in a marked increase in interleukin-8 release that was partially blocked by coincubation with alpha-melanocyte-stimulating hormone in a dose-dependent manner. Taken together, we show here that the melanocortin-1 receptor is expressed in vitro and in situ in human sebocytes. By modulating interleukin-8 secretion, alpha-melanocyte-stimulating hormone may act as a modulator of inflammatory responses in the pilosebaceous unit.

Binding and growth promoting effects of insulin, insulin analogues modified in the B chain, proinsulin, insulin-like growth factor-I and -II were studied in cultured rat aortic smooth muscle cells. Specific binding of 125I-insulin was 0.9 +/- 0.2% of total 125I-insulin added, and the IC50-value was estimated to 8.9 pmol/l. The insulin analogue B10 Asp tended to be more potent than insulin in displacing 125I-insulin, B28 Asp was equipotent, B9 Asp/B27 Glu was approximately 100 times less potent and insulin-like growth factor-I more than 1000 times less potent than insulin. Specific binding of 125I-insulin-like growth factor-I after 4 h incubation at 10 degrees C was five times higher than the specific binding of insulin (4.4 +/- 0.4% of total 125I-insulin-like growth factor-I added), and the IC50-value was 0.3 nmol/l. Insulin was approximately 500 times less potent than insulin-like growth factor-I in displacing 125I-insulin-like growth factor-I. The insulin analogue B10 Asp was slightly more potent and analogue B28 Asp was equipotent with insulin. Analogue B9 Asp/B27 Glu was ten times less potent and proinsulin was more than ten times less potent than insulin. The order of potency was similar for 3H-thymidine incorporation into DNA: insulin-like growth factor-I greater than B10 Asp greater than insulin-like growth factor-II greater than insulin greater than or equal to B28 Asp greater than B9 Asp/B27 Glu greater than proinsulin. The maximal effect of insulin-like growth factor-I on 3H-thymidine incorporation was 71 +/- 16% higher than the maximal effect of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)