Evidence for a nonprolactin, non-growth-hormone mammary mitogen in the human pituitary gland

To determine whether the human pituitary contains a previously unidentified, nonprolactin (non-hPRL), non-growth-hormone (non-hGH) factor capable of stimulating mammary development, we tested the effects of whole human pituitary extract (hPE) and pituitary extracts depleted of hPRL and hGH ("stripped hPE") in hypophysectomized, castrated estradiol (E2)-treated male rats and rhesus monkeys. Both whole and stripped hPE significantly stimulated rat mammary development (mean scores = 3.3 and 2.0, respectively, on a scale ranging from 0 to 4) in comparison with controls (mean score = 1.0). Mammary development was not due to minute concentrations of hGH or hPRL remaining in stripped hPE because 30- to 100-fold higher concentrations of hGH (Genentech) and 1000-fold higher concentrations of hPRL were required to stimulate significant mammary development. Non-pituitary extracts of human ovary, muscle, and serum, and bovine serum albumin did not stimulate rat mammary gland growth. Trypsin destroyed the mammary mitogenic activity of whole hPE, indicating that the unidentified factor is likely a protein. Mammary growth and development were also stimulated in hypophysectomized, E2-treated monkeys by stripped hPE (mean histological score = 3.25 vs. 1.35 in control animals). Monkeys receiving stripped hPE had undetectable levels of hGH and hPRL in serum sampled over a 24-hr period. These findings suggest that the human pituitary contains a non-hPRL, non-hGH factor that stimulates mammary growth and may be important in normal mammary growth and development and perhaps in breast cancer.