Human breast cancer: Concerted role of diet, prolactin and adrenal C₁₉‐Δ⁵‐steroids in tumorigenesis

Abstract

The low incidence of breast cancer in Japan disappears within 2 generations in migrant Japanese in the USA. This is of fundamental importance if we are to understand, and perhaps reverse, the high rate seen in Western countries. Diet is the most likely factor involved, and a review of the topic of diet, body mass index, and gain in adult body mass, supports a relationship between these factors and breast-cancer risk in post-menopausal, but not pre-menopausal, women. A direct link between nutritional factors and secretion of the hormones prolactin and dehydroepiandrosterone sulfate is proposed. An estrogen 5-androstene-3 beta, 17 beta-diol is formed peripherally from the latter steroid, and in Western women attains a blood concentration at which it is biologically active. Thus diet/fat provides factors, viz., fatty acids, prolactin and estrogen, which in concerted fashion provide a milieu conducive to mammary tumorigenesis.

Estrogens of multiple classes and their role in mental health disease mechanisms

“…Low dopamine levels (associated with depression) also relieve dopamine’s suppressive effect on PRL secretion in the pituitary, thus perhaps compounding adverse effects on mood. Estrogen-induced cell proliferation is also part of the normal response of the pituitary and many other reproduction-related tissues 73,74. Estrogen exposures at the wrong levels or of inappropriate types can cause disregulated proliferation, and even produce tumors of those tissues,75–77 including the pituitary;78 behavioral issues are compounded if these tumors are prolactinomas.…”

DHEA: A Biologist's Perspective

“…Certain groups of women—European/American versus Asian/African and high versus low calorie intake—may be at increased risk of breast cancer because of higher amounts of body fat, particularly during adolescence and postadolescence, and thereby higher aromatase and local estrogen formation 52, 78, 79 . Estradiol, estrone, and androstenediol are active estrogens that act in tumor initiation and/or growth of small tumors; when tumors are larger they may remain estrogen‐dependent or progress to estrogen‐independence 80 . The role of androgens per se in breast cancer development and growth is unclear 81 .…”

Nongenomic actions of estradiol compared with estrone and estriol in pituitary tumor cell signaling and proliferation

“…In addition, limited estrogen-induced cell proliferation is part of the normal response of the pituitary but can also produce pituitary tumors (22). PRL is believed to be a growth factor for many tissues, including breast and prostate (23,24), so its overproduction or excessive release by estrogens could lead to pathologies or tumors of these target tissues (25). We have studied membrane-initiated, E 2 -induced mechanistic and functional actions in a rat pituitary tumor cell subline (GH3/B6) for several years, and we (26,27) recently demonstrated that representatives of another class of so-called weak estrogens (as defined via the genomic mechanism; environmental estrogens) can cause potent nongenomic signaling effects in these cells whenever the membrane estrogen receptor is expressed at high levels.…”