In the present study we determined whether the fetus and estrogen affect maternal serum concentrations of GH, insulin-like growth factor-II (IGF-II), and epidermal growth factor (EGF) and placental IGF-II formation in pregnant baboons. The objective was to ascertain whether the previously reported increase in placental formation and serum concentrations of IGF-I induced by removal of the fetus and, thus, estrogen in pregnant baboons was mediated by GH and whether it was specific for IGF-I. On day 100 of gestation (term is 184 days), fetuses were removed, and placentas were left in situ, i.e. fetectomy. After fetectomy, baboons received pellets of aromatizable androstenedione (50-150 mg every 10 days, sc; n = 8), were injected with estradiol (E2) benzoate (0.50-2.5 mg/day, sc; n = 8), or were not further treated (n = 6) on days 101-159 of gestation. Placental cells obtained on day 160 were dispersed in 0.1% collagenase, isolated via 50% Percoll centrifugation, then incubated for 24 h at 37 C in medium 199. Maternal serum E2 concentrations increased with advancing gestation in intact baboons, were decreased by 79% after fetectomy and, thus, removal of adrenal C-19 steroid estrogen precursors, and restored by androstenedione or E2 treatment after fetectomy. Mean serum GH was 20.2 +/- 0.6 ng/ml on days 101-160 in untreated intact animals. Fetectomy decreased (P less than 0.001) GH levels to 12.1 +/- 0.5 ng/ml. Androstenedione or E2 treatment after fetectomy restored serum GH to 20.8 +/- 1.1 and 22.4 +/- 0.6 ng/ml, respectively. Serum IGF-II was 1406 +/- 54 ng/ml on days 101-160 in controls and decreased (P less than 0.001) rapidly after fetectomy to a value (305 +/- 16) that was 78% lower than that in untreated baboons. Androstenedione or E2 treatment after fetectomy had no effect on the fetectomy-induced decrease in IGF-II levels. In vitro secretion of IGF-II by placental trophoblasts of fetectomized baboons (10.3 +/- 0.6 ng/ml.24 h) was 88% lower (P less than 0.001) than that in controls (85.6 +/- 15.7). Despite androstenedione or E2 treatment after fetectomy, placental IGF-II production remained low (9.2 +/- 1.1 and 8.8 +/- 0.4 ng/ml.24 h, respectively). The overall mean maternal serum EGF concentration was 379 +/- 20 pg/ml in the second half of baboon pregnancy. Fetectomy or treatment with androstenedione or E2 had no effect on serum EGF levels.(ABSTRACT TRUNCATED AT 400 WORDS)