Breast development
Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a female's life.
It occurs across several phases, including prenatal development, puberty, and pregnancy. At menopause, breast development ceases and the breasts atrophy. Breast development results in prominent and developed structures on the chest known as breasts in primates, which serve primarily as mammary glands. The process is mediated by an assortment of hormones (and growth factors), the most important of which include estrogen, progesterone, prolactin, and growth hormone.
Biochemistry
Hormones
The master regulators of breast development are the steroid hormones, estrogen and progesterone, growth hormone (GH), mostly via its secretory product, insulin-like growth factor 1 (IGF-1), and prolactin.[1] These regulators induce the expression of growth factors, such as amphiregulin, epidermal growth factor (EGF), IGF-1, and fibroblast growth factor (FGF), which in turn have specific roles in breast growth and maturation.[1]
At
Despite the apparent necessity of GH/IGF-1 signaling in pubertal breast development however, women with
Development of the breasts during the prenatal stage of life is independent of
Progesterone, in conjunction with GH/IGF-1 similarly to estrogen, affects the development of the breasts during puberty and thereafter as well.
During
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.[37][46][48][49] At least one way that they do this is by reducing the expression of the estrogen receptor in breast tissue.[48][49][50] 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.[37] The combination of much higher levels of androgens (about 10-fold higher) and much lower levels of estrogen (about 10-fold less),[51] 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,[52] are why males generally do not grow prominent or well-developed breasts relative to females.[46][53]
Calcitriol, the hormonally active form of vitamin D, acting through the vitamin D receptor (VDR), has, like the androgens, been reported to be a negative regulator of mammary gland development in mice, for instance, during puberty.[41] VDR knockout mice show more extensive ductal development relative to wild-type mice,[54] as well as precocious mammary gland development.[55] In addition, VDR knockout has also been shown to result in increased responsiveness of mouse mammary gland tissue to estrogen and progesterone, which was represented by increased cell growth in response to these hormones.[54] Conversely however, it has been found that VDR knockout mice show reduced ductal differentiation, represented by an increased number of undifferentiated TEBs,[56] and this finding has been interpreted as indicating that vitamin D may be essential for lobuloalveolar development.[40] As such, calcitriol, via the VDR, may be a negative regulator of ductal development but a positive regulator of lobuloalveolar development in the mammary gland.[57]
A possible mechanism of the negative regulatory effects of the VDR on breast development may be indicated by a study of
Growth factors
Estrogen, progesterone, and prolactin, as well as GH/IGF-1, produce their effects on breast development by modulating the local expression in breast tissue of an assortment of
Based on research with
Elevated levels of HGF and, to a lesser extent, IGF-1 (by 5.4-fold and 1.8-fold, respectively), in breast stromal tissue, have been found in
Lactation
Upon
Breast size and cancer risk
Some factors of breast morphology, including their density, are clearly implicated in breast cancer. While breast size is moderately heritable, the relationship between breast size and cancer is uncertain. The genetic variants influencing breast size have not been identified.[82]
Through
Circulating IGF-1 levels are positively associated with breast volume in women.
Genetic variations in the androgen receptor (AR) have been linked to both breast volume (as well as body mass index) and breast cancer aggressiveness.[86]
COX-2 expression has been positively associated with breast volume and inflammation in breast tissue, as well as with breast cancer risk and prognosis.[61]
Rare mutations
Women with CAIS, who are completely insensitive to the AR-mediated actions of androgens, have, as a group, above-average sized breasts. This is true despite the fact that they simultaneously have relatively low levels of estrogen, which demonstrates the powerful suppressant effect of androgens on estrogen-mediated breast development.[37]
Aromatase excess syndrome, an extremely rare condition characterized by marked hyperestrogenism, is associated with precocious breast development and macromastia in females and similarly precocious gynecomastia (women's breasts) in males.[87][88][89] In complete androgen insensitivity syndrome, a condition in which the AR is defective and insensitive to androgens, there is full breast development with breast volumes that are in fact above average in spite of relatively low levels of estrogen (50 pg/mL estradiol).[37] In aromatase deficiency, a form of hypoestrogenism in which aromatase is defective and cannot synthesize estrogen, and in complete estrogen insensitivity syndrome, a condition in which ERα is defective and insensitive to estrogen, breast development is completely absent.[90][91][92]
See also
References
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Further reading
- Hovey, Russell C.; Aimo, Lucila (2010). "Diverse and Active Roles for Adipocytes During Mammary Gland Growth and Function". Journal of Mammary Gland Biology and Neoplasia. 15 (3): 279–290. PMID 20717712.
- Sun, Susie X.; Bostanci, Zeynep; Kass, Rena B.; Mancino, Anne T.; Rosenbloom, Arlan L.; Klimberg, V. Suzanne; Bland, Kirby I. (2018). "Breast Physiology". The Breast. pp. 37–56.e6. ISBN 9780323359559.