Role of Sex Steroid Hormones in Normal Mammary Gland Function

Haslam, Sandra Z.

doi:10.1007/978-1-4899-5043-7_15

Cited by 32 publications

(16 citation statements)

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“…It seems that cell proliferation occurs at a different time in each part of the nipple during the reproductive cycle. The mammary gland changes histologically during the reproductive cycle, and this process is regulated by many growth factors [7,5,15]. It has been reported that the role of proliferation of mammary epithelial cells increases bimodally; the highest relative number of dividing cells is found at an early stage (day 4) of pregnancy with a smaller peak on day 12 [1,17].…”

Section: Discussionmentioning

confidence: 99%

Histological Changes in Mouse Nipple Tissue during the Reproductive Cycle.

Toyoshima

Ohsako

Nagano

et al. 1998

The Journal of Veterinary Medical Science

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ABSTRACT. To obtain detailed information about the histological changes occurring in the mouse nipple during the reproductive cycle, we examined and quantified the S-phase of cell by immunohistochemical staining with bromodeoxyuridine (BrdU), and analysed histologically the subepithelial fibrous elements. The nipple markedly increased in size dramatically on days 15-18 of pregnancy. The densities of cells in the epidermis and dermis were very high during the early stages of pregnancy but low during lactation. In the epithelium of the lactiferous sinus, the densities of cells did not differ significantly among stages. The BrdU antibody labeling revealed a number of BrdUpositive cells in the basal layer of the epidermis and epithelium of the lactiferous sinus. The ratios of BrdU-positive cells to total cells in the epidermis and the epithelium of the lactiferous sinus were highest on day 15 and day 10 of pregnancy, respectively. After lactation, however, the ratios were similar to those in the virgin stage. No significant differences were detected in the dermis among all stages. The number of collagen and elastic fibers increased during lactation. These results indicate that cells in the epidermis and lactiferous sinus proliferated actively from day 10 to day 15 of pregnancy. The observation that cellular proliferation in the epithelial system of the nipple was stimulated at the early stage of pregnancy, while the dermis has two growth phases, with cellular proliferation during pregnancy and an increase in extracellular matrix during lacation, suggests that these two phenomena might be regulated by different factors. MATERIALS AND METHODS Animals:The Jcl-ICR strain mice used in this study were bred and maintained as a closed colony in our laboratory. They were all housed in an environmentally controlled airconditioned room (temperature: 23 ± 3°C, humidity: 60 ± 10%, light-dark cycle: 12-12 hr) and given a commercial diet (MF, Oriental Yeast Co., Tokyo) and tap water ad libitum. A total of 33 female mice (80-day-old) were mated with males of the same age, and the day when a vaginal plug was found was determined as day 0 of pregnancy. They were divided into 11 groups; i. e. virgin, days 5, 10, 15 and 18 of pregnancy, days 5, 10, 15 and 20 of lactation, days 5 and 10 of post-weaning. Each group consisted of 3 mice. At the lactating stage, each dam was housed with her 10 pups and separated from the young for 30 min before sampling.Administration of BrdU: BrdU (50 mg/kg b.w., Sigma, MO) was injected intraperitoneally into female mice at each reproductive stage. One hour after the injection, the nipples were excised under sodium pentobarbital anesthesia and fixed with Bouin's solution for 2 hr at room temperature. Mice have 3 pairs of thoracic and 2 pairs of abdominoinguinal nipples, and the first left abdomino-inguinal nipple was examined. The specimens were routinely embedded in paraffin and longitudinal sections 3 µm thick were cut.Immunohistochemical staining: To detect the S-phase cells, BrdU administration and an...

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Section: Discussionmentioning

confidence: 99%

Histological Changes in Mouse Nipple Tissue during the Reproductive Cycle.

Toyoshima

Ohsako

Nagano

et al. 1998

The Journal of Veterinary Medical Science

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“…With the onset of puberty at 4-to 5-week of age, the estrogen produced by the ovaries stimulated ductal elongation by increasing the level of epithelial and stromal cell proliferation in the end buds and surrounding stroma, respectively. The actions of the ovarian steroid hormones on ephithelial and stromal cells in the MG depend on the presence of their nuclear ER and progesterone receptors (PR) [30]. Immunohistochemical comparisons between the mammary or uterus sections were carried out using the appropriate antibodies for ER, PR, and PRLR expressed in a PND 41 MG and uterus (Figs.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Gestational Exposure to Nonylphenol Causes Precocious Mammary Gland Development in Female Rat Offspring

Moon

Han

Shin

et al. 2007

Journal of Reproduction and Development

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Abstract. This study examined whether or not exposure to 4-nonylphenol (NP) during late gestation affects reproductive and mammary development in the offspring of female rats. Time pregnant Long Evans rats were gavaged with NP (10 or 100 mg/kg), atrazine (ATR, 100 mg/kg), or corn oil on gestation days 15-19. The uterus weights of the NP (100 mg/kg/d)-exposed pups were higher than those of the controls but the weights of the other organs were unchanged. Delayed mammary gland (MG) development was detected in the ATR pups on PND 4 and persisted through to PND 66. The high dose NP pups had advanced lobular development of their MG on PND 22, while the glands from the low dose NP pups were no different morphologically from the controls. Immunohistochemical comparisons of the mammary sections from PND 41 demonstrated low levels of estrogen receptor (ER) staining in the control gland stroma and epithelium but higher levels in the tissue of the pups exposed to NP and ATR. ATR also elevated ER in the stroma surrounding the epithelial layer of the terminal end buds. The level of progesterone receptor (PR) staining was markedly lower in the epithelium of the 100 mg/kg NP glands vs. the control glands. However, PR was present at high levels in the epithelium of the 10 mg/kg NP glands and was even more prominent in the ATRexposed ductal epithelium and fat cell nuclei. The level of prolactin staining was only elevated in glands containing lobule areas (NP-exposed) compared with the control levels. These results suggest that NP and ATR have opposite effects on the development of MG after gestational exposure. Exposure to them during the critical period of epithelial outgrowth altered the receptor levels of mammary progesterone and prolactin and might contribute to the differences in the mammary morphology at PND 41. Key words: 4-Nonylphenol (NP), Atrazine, Endocrine disruptor, Hormone receptor, In utero exposure, Mammary gland, Rat (J. Reprod. Dev. 53: [333][334][335][336][337][338][339][340][341][342][343][344] 2007) he branched-chain isomer 4-nonylphenol (NP) is metabolized microbiologically from nonionic surfactants, 4-nonylphenol ethoxylates [1,2], and exhibits estrogenic eff e c t s b y s t i m u la t i n g expression of the estrogen-responsive vitellogenin gene in fish [3][4][5] and growth of human breast c a n c e r M C F -7 c e l l s [ 6 ] . N P a l s o e x e r t e d uterotrophic activity in immature and mature ovariectomised female rats and induced early onset of vaginal opening in a 20-day pubertal assay [7-

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“…In general, estrogens are responsible for growth of mammary ducts and progesterone is necessary for lobuloalveolar growth in the mouse (72); however, a direct mitogenic effect of estrogens on the mammary gland has not been clearly demonstrated (73). A postulated mechanism is that estrogens stimulate secretion of growth factors such as EGF (74) or other growth factors of mammary or extramammary origin that might sensitize the mammary gland to mitogenic factors (73,75 (76,77). The mammogenic effects of ovarian steroids are largely dependent on the integrity of the pituitary gland, because the effects of estrogen and progesterone cannot be demonstrated in hypophysectomized animals (78).…”

Section: Prenatal and Postnatal Developmentmentioning

confidence: 99%

“…Estrogens are critically involved in mammary gland development and are also essential for eliciting a tumorigenic response with chemical or physical carcinogens (47,197). Estrogens act on mammary epithelial cells through three different mechanisms: a direct receptor-mediated effect, a mammary stroma-mediated effect, and an in vivo stimulation of pituitary PRL levels, which in turn, stimulates lobuloalveolar development in the mammary gland (67,76). Estradiol is the most potent and abundant estrogenic hormone and is responsible for the beginning of estrus.…”

Section: Ovarian Steroid Hormones and Growth Factorsmentioning

confidence: 99%