Prepubertal and Pubertal Gynecomastia

Physiology and molecular mechanisms Gynecomastia is defined as the growth of the male mammary gland to become palpable and/or visible. During embryogenesis, the differentiation of the mammary gland and surrounding estroma, as well as the areola and the nipple, is similar in the two sexes. It is well established that estrogens stimulate breast growth. The production of estrogens during pregnancy is very high. For this reason, breast development is frequently present at birth in the two sexes. Furthermore, several growth factors (EGF, TGFα, IGF-1), progesterone, and GH have also been implicated in mammary growth. However, little is known about the mechanisms modulating differentiation and development of the mammary gland in fetal life [1]. The gonadal activity of the embryonic and fetal testes with their high secretion of testosterone do not generate a sexual dimorphism in the breast development of the newborn. This is interesting, because it has been speculated that in the absence of androgen action, such as in the complete form of the androgen insensitivity syndrome, mammary over development is observed [2]. Moreover, it is generally accepted that the estrogen/androgen balance is an important factor in adult gynecomastia [3, 4], and some experimental evidence indicates that testosterone inhibits estrogen-induced mammary epithelial cell proliferation and suppresses estrogen receptor expression [5]. Even though many questions remain, the central role of estrogens and its receptors on mammary development is well accepted.