Clinical Studies

Mammary Gland Development And Phytoestrogens (Botanical photos)

Introduction

In literature no data can be found o­n the specific effects sorted by phytoestrogen with respect to breast development and enlargement except for the unwanted breast development in male, a phenomenon called gynecomastia.

Since phytoestrogen posses significant estrogenic properties and therefore may act like endogenous estrogens this mini review will shortly introduce the natural mammary gland development followed by an introduction o­n the phytoestrogens themselves.

Early in foetal life epithelial cells, derived from the epidemis in the area that will later become the areola, proliferate into the underlying mesenchyme. In the human, 20 or so short cords are formed and eventually develop lumina to become ducts that are connected to the nipple and open to the surface. Surrounding the ducts is a network of myeloepithelial cells, destined ultimately to serve in the expulsion of milk. In the later stages of gestation the blind ends of the ducts bud to form alveolar structures and a small amount of secretory activity occurs.

The results in the formation of so called witchs milk, which can be expressed from the breasts of most full term infants for 1-7 weeks thereafter. Subsequently, with the decline of circulating foetal prolactin and in the absence in the infant of estrogen and progesterone of placental origin, the breast regresses to a resting stage composed of a small number of scattered ducts. Such regression may no be complete until months after birth.

In several species there is sexual dimorphism in the embryogenesis of the excretory duct system. In human beings there does appear to be any histologic or functional difference in the breasts of girls and boys before the o­nset of puberty. Shortly before human menarche, with increased secretion of ovarian estrogen, lengthening and branching of the ducts begin in the female breast, accompanied by budding of the terminal ends and increased formation of underlying fat and connective tissue. With the o­nset of menses, further growth takes place in cyclic fashion some regression occurring at the end of each cycle. Mammary gland development is under multihormonal control involving functional interplay between ovary and pituitary.

The co ordinated action of estrogen, prolactin, progesterone, glucocorticoids., insulin, growth hormone, and thyroid hormone are involved. Classical endocrine ablation/hormone replacement studies demonstrate that ovarian estradiol is critical to the major phases of mammary development; ductal elongation during puberty and lobuloalveolar development during pregnancy. However the effects of estrogens o­n mammary growth appeared to require a functional pituitary gland.

Therefore, estrogens may contribute to mammary development by acting directly o­n the mammary gland and or by indirect endocrine action of the hypothalamic/pituitary/gonadal axis. The alveolar development is also controlled by prolaction and progesterone; lactation is mediated by prolactin. Estrogen, as said before, is ineffective in the absence of anterior pituitary hormones. Administration of estrogens to intact animals promotes the formation if lactotropic cells in the pituitary and increases the secretion of prolaction and growth hormone. In the presence of these two hormones, estrogen acts to promote ductal development in the breast

Although estrogen prepares the breast for eventual milk formation, it also acts to inhibit lactation and in their respect acts as a prolactin antagonist. It is largely because of the high levels of circulating estrogen and progesterone that women do not lactate during pregnancy, and the abrupt withdrawal of these tow hormones with the termination of pregnancy triggers the o­nset of lactation. Estrogen also acts to regulate the number of prolactin receptors in breast tissue.

Phytoestrogens

Phytoestrogens are a diverse group of nonsteroidal plant components that can behave as estrogens and occur naturally in most plants, fruits, and vegetables. They were first noted in 1926 to have estrogenic activity. In particular the position and the distance of the hydroxyl substitutes enables the molecule to bind to estrogen receptors. They bind to both receptor types, the estrogen alpha and the estrogen B receptor.

Many phytoestrogens seems to have higher affinity for the ERB receptor than steroidal estrogens, which suggests that they may exert there actions through distinctly different pathways. However, despite their ability to bind to the estrogen receptor, they are much weaker then than human estrogens, with 105 times less activity. Phytoestrogens seem to possess both estrogenic as well as antiestrogenic activity. Whether they act primarily as and estrogen or as an antiestrogen seems to depend o­n the amount of endogenous estrogens the number and type of estrogen receptor and last but not least the tissue type in which the receptors are expressed. Phytoestrogens are frequently detected in man in much higher quantities than endogenously produced estrogens.

There are three main types of phytoestrogens: the isoflavones (the most potent), coumestrans, and lignans. There are more than 1000 types of isoflavones, but the most commonly investigated are genistein and daidzein, which are also thought to have the highest estrogenic activity. Thery are found in legumes such as soy, chickpeas, clover, lentils and beans. The isoflavones are fbound to glucose, and when ingested by humans, they are enzymatically cleaved in the gut to the active forms.

The metabolism of the phytoestrogens varies from person to person, and there also seems to be a sex difference, with women appearing to metabolise them more efficiently. The lignans (enterolactone or enterodiol) are found in flaxseed, lentils, whole grains, beans fruits and vegetables. Other classes which are more rarely ingested, are the coum (found in sprouting plants), flavones, flavanones, chalcones, terpenoids, and saponins.

Safety

With respect to adverse effects of phytoestrogens in general no specific data are available and this needs further investigation. Thus far mainly beneficial effects were noted o­n basis of epidemiological studies. It was observed that the rates of colon., prostate, and breast cancers were much lower in Japan and other Southeast Asian societies than in the United States. The same was found for cardiovascular diseases and with respect to menopausal symptoms it was found that Asian women had approximately 10% the incidence of hot flashes that American women had (these results, however, should be corrected for cultural definitions are beliefs)

Since Japnese migrating to the US developed an increased incidence of western diseases within 1 or 2 generations, it was concluded that the genetic background could not be the o­nly factor and attention was turned to the diet. o­ne of the most significant differences observed was the high quantity of soy in the Asian diet. The daily soy intake in an Asian population is 20-50 times higher than in an American population. Soy contains high levels of phytoestrogens, particularly isoflavones (genistein, daidzzein). Since no particular adverse effects are observed in the Asian population int ca be concluded that up to these levels (20-50 mg/d of soy) the use is safe.

Breast development in male, however, is seen as an unwanted effect and medically defined as gynecomastia. Male breast development can be caused by the intake of estrogenic drugs, from industrial exposure or from exporeue to estrogen enlargement of breast tissue from lipomastia,. In particular in oeverweight men. In this regard it is important to realise that the bulk of breast tissue in normal women and in most men is adipose tissue.

References

1.  Frantz. A.G., and Wilson. J.D. 1998 in : Williams Textbook of Endocrinology. Sauders 9^th edition Eds, Wilson, Foster, Kronenberg, and Larsen. PP 877 900

2.  Thompson, L.U., Robb, P, Serraino, M 1991: Mammalian lignan production from various foods. Nutr. Cancer: 45 53

3.  Murkies, A.L. Wilcox. G., Davis R.S. 1998: Phytoestrogens. J Clin Endocrin Metab: 297 303.

4.  Setchell, K.D. 1998: Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr 68 (suppl) 1333S 1 346S.

5.  Price. K.R., Fenwick, G.R.: Naturally occurring estrogens in foods a review. FooAddit Contarn 2:73 106

.