Development of the mammary gland and lactation

Rillema, James A.

doi:10.1016/1043-2760(94)90011-6

Cited by 42 publications

(22 citation statements)

References 28 publications

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“…Tissues of the female reproductive system require the coordinated actions of pituitary, ovarian, and adrenal hormones and growth factors for normal development (1). During fetal development, growth factors seem to play a major role in mammary gland development, whereas estrogen, glucocorticoids, and growth hormone are vital for mammary development during puberty (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

“…During fetal development, growth factors seem to play a major role in mammary gland development, whereas estrogen, glucocorticoids, and growth hormone are vital for mammary development during puberty (2)(3)(4). Insulin, thyroid hormone, and growth factors such as IGF-I, EGF, PDGF, and the TGFs are also important during pubertal development (1)(2)(3)(4). These same factors and additional hormones including progesterone and prolactin contribute to pregnancy-induced mammary growth (5).…”

Section: Introductionmentioning

confidence: 99%

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Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model.

Neuenschwander¹,

Schwartz²,

Wood³

et al. 1996

J. Clin. Invest.

197

100

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Development of the mammary gland during puberty, pregnancy, and lactation is controlled by steroid and peptide hormones and growth factors. To determine the role of the insulin-like growth factors (IGFs) in this process we developed a transgenic model using the whey acidic protein (WAP) gene to direct expression of rat IGF-I and human IGF binding protein-3 (IGFBP-3) to mammary tissue during late pregnancy and throughout lactation.High levels of expression of transgenic IGF-I and IGFBP-3 were seen in lobular-alveolar cells by in situ hybridization. There was no obvious effect on mammary development during pregnancy and lactation; indeed, mothers were capable of nursing their pups normally and the only structural difference seen in the mammary glands at peak lactation was an overall smaller size of the alveoli. We also evaluated the role of IGF-I and IGFBP-3 in the remodeling of mammary tissue during involution. Compared with control animals, the process of involution was modified in both transgenic lines. The degree of apoptotic cells was lower in the WAP-IGF-I and WAP-BP-3 expressing mice. In addition, there was a more quiescent pattern of involution with residual lobular secretory ability and a muted host inflammatory reaction with fewer lumenal microcalcifications.These results demonstrate that IGF-I and IGFBP-3 may modulate the involutionary process of the lactating mammary gland. ( J. Clin. Invest. 1996. 97:2225-2232).

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model.

Neuenschwander¹,

Schwartz²,

Wood³

et al. 1996

J. Clin. Invest.

197

100

View full text Add to dashboard Cite

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“…These main stages of mammary growth and differentiation are dependent on endocrine, paracrine, and autocrine control mechanisms which involve complex interactions between steroid hormones, polypeptide hormones, and growth factors , Forsyth 1989, Rillema 1994. The major player in mammary gland growth and development, as well as in lactation, is widely considered to be prolactin (PRL) , Vonderhaar 1987.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of the growth hormone receptor and growth hormone-binding protein in epithelia and stroma of the mouse mammary gland at various physiological stages

Ilkbahar

Thórdarson²,

Camarillo³

et al. 1999

Journal of Endocrinology

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Increasing evidence suggests that GH is important in normal mammary gland development. To investigate this further, we studied the distribution and levels of growth hormone receptor (GHR) and GH-binding protein (GHBP) in the mouse mammary gland. At three weeks of age, the epithelial component of the right fourth inguinal mammary gland of female mice was removed. These animals were then either maintained as virgins until they were killed or they were mated. One group of the mated mice was killed on day 18 of pregnancy and the remaining mated animals were allowed to carry their pups until term and were killed on day 6 of lactation. At the time of death, both the intact left and the de-epithelialized right mammary glands were collected from all three groups. Some of the intact glands served as a source of epithelial cells, free of stroma. The mRNA levels for GHR and GHBP were measured in intact glands, epithelia-cleared fat pads, and isolated mammary epithelial cells. GHR and GHBP mRNAs were expressed in both the mammary epithelium and stroma. However, the levels of both GHR and GHBP mRNAs were significantly higher in the stroma as compared with the epithelium component. This increase for both mRNAs was from 3-to 12-fold at each physiological state examined. In the intact gland, both GHR and GHBP transcripts were highest in virgins, declined during late pregnancy, and the lowest levels were found in the lactating gland. GHBP and GHR protein concentrations were also assessed in intact glands and epithelia-free fat pads. Similar to the mRNAs, GHR and GHBP protein levels (means ...) in intact glands were highest in virgin mice (0·891 0·15 pmoles/mg protein and 0·136 0·26 pmoles/mg protein respectively), declined during late pregnancy (0·354 0·111 pmoles/mg protein and 0·178 0·039 pmoles/mg protein respectively), and were lowest during lactation (0·096+0·037 pmoles/mg protein and 0·017+0·006 pmoles/mg protein respectively). Immunocytochemistry utilizing specific antisera against mouse (m) GHR and mGHBP revealed that the two proteins are localized to both the stroma and parenchyma of mouse mammary glands, with similar patterns of immunostaining throughout the different physiological stages analyzed. GHR immunolocalized to the plasma membrane and cytosol of mammary epithelial cells and adipocytes, whereas the GHBP immunostaining was nuclear and cytosolic. In conclusion, we report here that GHR and GHBP mRNAs and proteins are expressed in both the epithelium and the stroma of mammary glands of virgin, pregnant, and lactating mice. In intact glands, GHR and GHBP proteins, as well as their transcripts are higher in abundance in virgin relative to lactating mice. At all physiological stages, GHR and GHBP mRNA levels are higher in the stroma compared with the parenchyma. These findings indicate that the actions of GH in the mammary gland are both direct through its binding to the epithelia, and indirect by binding to the stroma and stimulation of IGF-I production which, in turn, affects mammary epithelial developme...

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“…Com plex molecular interactions are involved in the regu lation of lactation (Rillema, 1994). T h e initiation of lacta tion following parturition involves m an y endocrine changes, of which the reduced influence of sex steroid hor mones appears to be the most important (for review see Daniel and Silberstein, 1987;Rillema, 1994). LAR is expressed in brain and therefore could perhaps piay a role in the regulation of the appropriate hormone balance needed for proper mammary gland development and function.…”

Section: Alveoli In Nonlactating Lar ~ Femalesmentioning

confidence: 99%

“…Taken together, these observations suggest that L A R function is evoked relatively late in m a m m a r y gland development and that most likely the L A R " /_ pheno type is a combination of a loss of alveolar cells around partu rition and the inability of the remaining alveoli to undergo secretory differentiation. Com plex molecular interactions are involved in the regu lation of lactation (Rillema, 1994). T h e initiation of lacta tion following parturition involves m an y endocrine changes, of which the reduced influence of sex steroid hor mones appears to be the most important (for review see Daniel and Silberstein, 1987;Rillema, 1994).…”

Section: Alveoli In Nonlactating Lar ~ Femalesmentioning

confidence: 99%

Impaired mammary gland development and function in mice lacking the LAR receptor-like tyrosine phosphatase activity

1997

Trends in Genetics

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The LAR receptor-like protein tyrosine phosphatase is composed of two intracellular tyrosine phosphatase domains and a cell adhesion molecule-like extracellular region containing three immunoglubulin-like domains in combination with eight fibronectin type-III-like repeats. This architecture suggests that LAR may function in cellular signalling by the regulation of tyrosine phosphorylation through cell-cell or cell-matrix interactions. We used gene targeting in mouse embryonic stem cells to generate mice lacking sequences encoding both LAR phosphatase domains. Northern blot analysis of various tissues revealed the presence of a truncated LAR mRNA lacking the cytoplasmic tyrosine phosphatase domains and indicated that this LAR mutation is not accompanied by obvious changes in the expression levels of one of the LAR-like receptor tyrosine phosphatases PTP5 or PTPo\ LAR"''" mice develop and grow normally and display no appreciable histologi cal tissue abnormalities. However, upon breeding we observed an abnormal neonatal death rate for pups from LAR~;~ females. Mammary glands of LAR"7" females were incapable of delivering milk due to an impaired terminal differentiation of alveoli at late pregnancy. As a result, the glands failed to switch to a lactational state and showed a rapid involution postpartum. In wild-type mice, LAR expression is regulated during pregnancy reaching maximum levels around Day 16 of gestation. Taken together, these findings suggest an important role for LAR-mediated signalling in mammary gland develop ment and function.

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Development of the mammary gland and lactation

Cited by 42 publications

References 28 publications

Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model.

Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model.

Differential expression of the growth hormone receptor and growth hormone-binding protein in epithelia and stroma of the mouse mammary gland at various physiological stages

Impaired mammary gland development and function in mice lacking the LAR receptor-like tyrosine phosphatase activity

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