<P> Progesterone, in conjunction with GH / IGF - 1 similarly to estrogen, affects the development of the breasts during puberty and thereafter as well . To a lesser extent than estrogen, progesterone contributes to ductal development at this time, as evidenced by the findings that progesterone receptor (PR) knockout mice or mice treated with the PR antagonist mifepristone show delayed (albeit eventually normal, due to estrogen acting on its own) ductal growth during puberty and by the fact that progesterone has been found to induce ductal growth on its own in the mouse mammary gland mainly via the induction of the expression of amphiregulin, the same growth factor that estrogen primarily induces to mediate its actions on ductal development . In addition, progesterone produces modest lobuloalveolar development (alveolar bud formation or ductal sidebranching) starting at puberty, specifically through activation of PRB (and notably not PRA), with growth and regression of the alveoli occurring to some degree with each menstrual cycle . However, only rudimentary alveoli develop in response to pre-pregnancy levels of progesterone and estrogen, and lobuloalveolar development will remain at this stage until pregnancy occurs, if it does . In addition to GH / IGF - 1, estrogen is required for progesterone to affect the breasts, as estrogen primes the breasts by inducing the expression of the progesterone receptor (PR) in breast epithelial tissue . In contrast to the case of the PR, ER expression in the breast is stable and differs relatively little in the contexts of reproductive status, stage of the menstrual cycle, or exogenous hormonal therapy . </P> <P> During pregnancy, pronounced breast growth and maturation occurs in preparation of lactation and breastfeeding . Estrogen and progesterone levels increase dramatically, reaching levels by late pregnancy that are several hundred-fold higher than usual menstrual cycle levels . Estrogen and progesterone cause the secretion of high levels of prolactin from the anterior pituitary, which reach levels as high as 20 times greater than normal menstrual cycle levels . IGF - 1 and IGF - 2 levels also increase dramatically during pregnancy, due to secretion of placental growth hormone (PGH). Further ductal development, by estrogen, again in conjunction with GH / IGF - 1, occurs during pregnancy . In addition, the concert of estrogen, progesterone (again specifically through PRB), prolactin, and other lactogens such as human placental lactogen (hPL) and PGH, in conjunction with GH / IGF - 1, as well as insulin - like growth factor 2 (IGF - 2), acting together, mediate the completion of lobuloalveolar development of the breasts during pregnancy . Both PR and prolactin receptor (PRLR) knockout mice fail to show lobuloalveolar development, and progesterone and prolactin have been found to be synergistic in mediating growth of alveoli, demonstrating the essential role of both of these hormones in this aspect of breast development . Growth hormone receptor (GHR) knockout mice also show greatly impaired lobuloalveolar development . In addition to their role in lobuloalveolar growth, prolactin and hPL act to increase the size of the nipple - areolar complex during pregnancy . By the end of the fourth month of pregnancy, at which time lobuloalveolar maturation is complete, the breasts are fully prepared for lactation and breastfeeding . </P> <P> Insulin, glucocorticoids such as cortisol (and by extension adrenocorticotropic hormone (ACTH)), and thyroid hormones such as thyroxine (and by extension thyroid - stimulating hormone (TSH) and thyrotropin - releasing hormone (TRH)) also play permissive but less well - understood / poorly - characterized roles in breast development during both puberty and pregnancy, and are required for full functional development . Leptin has also been found to be an important factor in mammary gland development, and has been found to promote mammary epithelial cell proliferation . </P> <P> In contrast to the female - associated sex hormones, estrogen and progesterone, the male - associated sex hormones, the androgens, such as testosterone and dihydrotestosterone (DHT), powerfully suppress the action of estrogen in the breasts . At least one way that they do this is by reducing the expression of the estrogen receptor in breast tissue . In the absence of androgenic activity, such as in women with complete androgen insensitivity syndrome (CAIS), modest levels of estrogen (50 pg / mL) are capable of mediating significant breast development, with CAIS women showing breast volumes that are even above - average . The combination of much higher levels of androgens (about 10-fold higher) and much lower levels of estrogen (about 10-fold less), due to the ovaries in females producing high amounts of estrogens but low amounts of androgens and the testes in males producing high amounts of androgens but low amounts of estrogens, are why males generally do not grow prominent or well - developed breasts relative to females . </P>

Role of estrogen and progesterone in breast development