Gonadal and adrenal effects on hepatic epidermal growth factor receptor expression in a murine model.

We hypothesize that the actions of epidermal growth factor (EGF) may be modulated by changes in cell surface EGF receptor (EGF-R) expression under endocrine influences. Mouse liver cell membrane preparations were used in a RRA. During ontogenesis, both sexes showed a significant increase (P less than 0.005) in hepatic EGF-R numbers at puberty; however, males demonstrated significantly higher levels than females (P less than 0.005). Gonadectomy of adult males and females resulted in a significant (P less than 0.05) decrease and increase, respectively, in hepatic EGF-R expression. Prepubertal gonadectomy in both sexes resulted in EGF-R levels similar to those observed in adult females. Adrenalectomy of adult animals of both sexes had no effect on hepatic EGF-R numbers, but gonadectomy plus adrenalectomy virtually obliterated EGF-R expression. Short term treatment with testosterone of adult females or gonadectomized female and male mice significantly increased EGF-R numbers (P less than 0.05) to adult male levels. 17 beta-Estradiol given short term to adult males or gonadectomized male and female mice did not significantly alter EGF-R levels. EGF-R expression in androgen-insensitive male mice was significantly reduced (P less than 0.005) to female levels. We conclude that 1) hepatic EGF-R numbers increase post-pubertally in both sexes; 2) hepatic EGF-R expression is significantly stimulated by testosterone, and this effect depends on a functional androgen receptor; 3) the ovary has an inhibitory effect on adult hepatic EGF-R numbers; however, this effect does not appear to be mediated by estrogens; and 4) the adrenal gland has a stimulatory effect on adult hepatic EGF-R expression.