Role of receptors for epidermal growth factor and insulin-like growth factors I and II in the differentiation of rat mammary glands from lactogenesis I to lactogenesis II.

In addition to ovarian steroids and lactogenic hormones from the placenta and pituitary, growth factors control the growth and differentiation of mammary glands. Lactogenesis II at the end of pregnancy is under the control of progesterone. Ovariectomy results in a significant decrease in the number of receptors for epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) and an increase in IGF-II binding sites in mammary gland acini of rats, without affecting the affinity for their respective ligand. Although concentrations of EGF, IGF-I and IGF-II receptors are regulated by oestradiol and progesterone, replacement treatment with ovarian steroids after ovariectomy showed that receptor concentrations do not mediate the restraint on lactogenesis. Progesterone treatment, which inhibits the onset of lactogenesis II, did not restore EGF receptor concentrations to control values, and the presence of oestradiol was required to reverse the effect of ovariectomy. Oestradiol, which potentiates the effect of ovariectomy on milk synthesis, increases IGF-I receptor concentrations. IGF-II receptor concentrations, after the different steroid treatments, were consistent with the steroid effect on milk synthesis. The changes observed in the concentrations of these growth factor receptors at the onset of mammary gland secretion are not considered to affect the progesterone block to lactogenesis II, but rather are a consequence of the shift of the hormonal and, hence, physiological status of the gland.