Hormonal changes during the first year of oestrogen treatment in constitutionally tall girls.

OBJECTIVE: Oestrogens are used to inhibit growth in girls with constitutionally tall stature. We studied the changes in different hormones that accompany such therapy. SUBJECTS AND METHODS: In this longitudinal study we examined the levels of total insulin-like growth factor-I (IGF-I), free thyroxine (FT(4)), thyrotrophin (TSH), testosterone, dehydroepiandrosterone sulphate (DHEA-S), cortisol and prolactin in two groups of girls receiving ethinyloestradiol at a dose of either 0.1mg daily (group A, n=22) or 0.2mg daily (group B, n=36). Hormonal measurements were performed at start of therapy and after 3, 6 and 12 months. RESULTS: In both groups the levels of IGF-I, testosterone and DHEA-S were reduced while the concentrations of cortisol and prolactin were increased. The pituitary-thyroid axis was not significantly affected by this therapy. The girls receiving 0.2mg ethinyloestradiol daily had lower IGF-I levels after 12 months of therapy and had higher serum prolactin concentrations than the girls treated with 0.1mg daily. The reduction in predicted height and the advancement in bone age were similar in both groups. CONCLUSIONS: Therapy with pharmacological doses of ethinyloestradiol changes the levels of several hormones including IGF-I, testosterone, DHEA-S, prolactin and cortisol but the role of the respective changes in the inhibition of growth is not clear. The suppression of DHEA-S levels by 40% suggests that the ovaries contribute significantly to the production of this hormone in pubertal girls.

Glucocorticoid-induced growth arrest of lung alveolar epithelial cells is associated with increased production of insulin-like growth factor binding protein-2.

Glucocorticoids have been shown to impair lung growth by altering development of the alveolar structure. To characterize the mechanisms involved in this process, we examined the effects of dexamethasone on proliferation of the stem cells of the alveolar epithelium, the type 2 cells. Treatment of type 2 cells with dexamethasone rapidly decreased DNA synthesis, and this effect was observed for concentrations less than 10(-8)M. Inhibition of cell proliferation by glucocorticoids was associated with a marked accumulation of insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) in the culture medium. Studies of the mechanisms involved in this accumulation indicated that it was associated with an enhanced production of IGFBP-2 and with a similar increase in the level of IGFBP-2 messenger RNA expression without any changes in its stability, as evaluated by actinomycin D experiments. Furthermore, transfection studies using plasmids conveying expression of luciferase gene transcribed from the fragment of rat IBFBP-2 promoter extending from +12 bp relative to the start of transcription plus 1.4 kilobases of the 5'-flanking sequence showed a stimulation of luciferase activity in cells treated with dexamethasone that was similar to the increase in IGFBP-2 messenger RNA and protein. Study of the other components of the IGF system also revealed induction of IGF-II expression upon treatment with dexamethasone. Together with other previously reported results using various modulators of type 2 cell proliferation, the present study strongly suggests that IGFBP-2 is likely to play an important role in the control of alveolar epithelial cell proliferation.