INSULIN-LIKE GROWTH FACTOR-I, BUT NOT GROWTH-HORMONE, HAS INVITRO PROLIFERATIVE EFFECTS ON NEONATAL FORESKIN FIBROBLASTS WITHOUT AFFECTING 5-ALPHA-REDUCTASE OR ANDROGEN RECEPTOR ACTIVITY

Clinical observation of patients with congenital growth hormone (GH) d eficiency and Laron-type dwarfism suggests that factors such as GH or insulin-like growth factor 1 (IGF-1) might, in addition to androgens, be needed for normal phallic growth. We speculated GH or IGF-1 might h ave direct actions on genital tissues and performed the present study to evaluate the in vitro effects of GH and IGF-1 on cultured neonatal foreskin fibroblasts. Cells derived from foreskins of normal newborns were studied between cell passages 6 and 15. Serum-free media with and without 100 ng/ml GH, IGF-1, or both were added 24 hours prior to and at the time of study. To determine the activity of 5-alpha-reductase (5-alpha-R), H-3-testosterone (T; 2 nM) was added, and 5-alpha-R activ ity was calculated as femtomoles H-3-dihydrotestosterone and H-3-andro stanediol produced/microgram DNA/hour. Androgen receptor (AR) binding was determined by the addition of H-3-dihydrotestosterone (dHT; 0.0312 5-0.5 nM) in the presence and absence of a 200-fold excess of unlabele d dHT. Specific binding was used in Scatchard analysis for determinati on of AR number (B(max)) and binding affinity (K(d)). The rate of DNA synthesis was determined by incorporation of H-3-thymidine (H-3-Thy) i nto trichloroacetic acid-insoluble material. DNA and protein content w ere determined on cell lysates. IGF-1, but not GH, had proliferative e ffects (significant increases in the rate of H-3-Thy incorporation, DN A, and protein content) but no effect on 5-alpha-R activity, B(max) or K(d). This suggests that IGF-1 has direct, in vitro, proliferative ef fects on genital tissue that are not mediated by changes in 5-alpha-R or AR.