Non-Lactogenic Effects of Growth Hormone on Growth and Insulin-Like Growth Factor-I Messenger Ribonucleic Acid of Rat Mammary Gland

Kleinberg, David L.; Ruan, Weifeng; Catanese, Veronica; Newman, Connie B.; Feldman, Mark

doi:10.1210/endo-126-6-3274

Cited by 99 publications

(40 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We have demonstrated the importance of synergy between E 2 and GH or IGF-I during pubertal mammary development in the rat (Kleinberg et al 1990, Feldman et al 1993, Ruan et al 1995. We have found that GH can induce IGF-I mRNA in the mammary fat pad, and IGF-I can then substitute for GH in stimulating TEB development in the presence of E 2 (Ruan et al 1992(Ruan et al , 1995.…”

Section: Discussionmentioning

confidence: 60%

“…We have shown that growth hormone (GH) is the pituitary factor essential for mammary development (Kleinberg et al 1990, Feldman et al 1993, and that the effect of GH is likely mediated by local production of insulin-like growth factor (IGF)-I (Ruan et al 1992(Ruan et al , 1995. Recent evidence indicates that GH exerts its effect within the stromal compartment of the mammary gland, suggesting that a paracrine event causes induction of terminal end buds (TEBs), and subsequent pubertal mammary development (Walden et al 1998).…”

Section: Introductionmentioning

confidence: 96%

“…The development of the rodent mammary gland is dependent on both steroid and pituitary hormones (Lyons et al 1958, Nandi 1958, Kleinberg et al 1990, Lyons 1993. We have shown that growth hormone (GH) is the pituitary factor essential for mammary development (Kleinberg et al 1990, Feldman et al 1993, and that the effect of GH is likely mediated by local production of insulin-like growth factor (IGF)-I (Ruan et al 1992(Ruan et al , 1995.…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

The effect of GH on estrogen receptor expression in the rat mammary gland

Feldman

Ruan²,

Tappin³

et al. 1999

Journal of Endocrinology

View full text Add to dashboard Cite

Both GH and insulin-like growth factor I (IGF-I) synergize with estrogen to induce normal mammary gland development. However, the nature of this synergy has not been explored. To gain insight into the mechanism of these interactions we have examined the effects of these substances on the estrogen receptor (ER). ER levels in the mammary gland cytosols from hypophysectomized and oophorectomized rats, were measured using two assay systems: a dextran-coated charcoal procedure to measure binding to radiolabeled steroid, and an immunologic assay employing a specific antibody to the receptor. In both assays, levels of ER were at or near baseline detection (1-2 ng/mg protein). Treating animals with either bovine or human GH significantly increased ER activity (P<0·001), whereas prolactin (PRL) and/or estradiol treatment had no effect. That this increase was at the level of transcription was demonstrated by reverse transcriptase/ polymerase chain reaction. Following a single injection of GH (50 µg), a substantial increase in ER mRNA was observed by 10 h, with levels returning to baseline within 24 h; a concomitant increase in ER itself was also observed at the 10 h time point. The effect of GH appeared to occur mainly in the mammary stroma, because there were no differences in GH stimulation of ER between gland-free and gland containing mammary fat pads. Furthermore, analysis of mammary gland ER by immunocytochemistry demonstrated that while ER was present in the epithelial cells of non-treated animals, only GH treated animals had ER clearly visible in both glandular and fat cells of the tissue. In contrast, treating animals with des(1-3)-IGF-I did not result in reproducible increases in ER, nor in the staining of fat cell nuclei for ER. These data demonstrate a specific GH effect on the ER in the mammary fat cell.

show abstract

Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

The effect of GH on estrogen receptor expression in the rat mammary gland

Feldman

Ruan²,

Tappin³

et al. 1999

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Some forms are lactogenic, and in some experimental animals GH is more potent than prolactin in stimulating mammary development (Kleinberg et al, 1990). The treatment of prepubertal girls with isolated GH deficiency by using recombinant hGH has been shown to accelerate the development of mammary tissue (Darendeliler et al, 1990).…”

Section: Interaction Between Igf and Oestrogen Receptorsmentioning

confidence: 99%

“…The researchers postulate that mammary cancers may develop autonomous synthesis of GH. As GH can stimulate mRNA of IGF1 in mammary tissue (Kleinberg et al, 1990) it is possible that it exerts a paracrine effect in mammary carcinogenesis by increasing IGF 1 availability (Feldman et al, 1993). This is in addition to a possible endocrine effect on bioavailable IGFI levels, because the serum GH level is correlated with the IGFI/IGFBP3 ratio (Juul et al, 1994).…”

Section: Interaction Between Igf and Oestrogen Receptorsmentioning

confidence: 99%

Breast cancer: further metabolic-endocrine risk markers?

1997

Br J Cancer

View full text Add to dashboard Cite

Summary There is evidence that increased oestrogen receptor (ER) expression in normal mammary epithelium may be a risk marker for the development of breast cancer. Insulin-like growth factor 1 (IGF1) is a potent inducer of mitosis and has been shown to synergize with oestrogen in stimulating the growth of human breast cancer in vitro. In these cells oestradiol has been shown to upregulate IGF Khan et al, 1994). ER expression in normal breast tissue is correlated with its proliferative activity and it has been postulated that the mitogenic activity of insulin-like growth factor 1 (IGF1) might interact with that of oestradiol in promoting breast cancer development after the initiation of carcinogenesis (Clarke et al, 1997). It is useful to summarize recent studies attempting to correlate measurements of ER and IGF1 with those of IGFI receptor (IGFR) and binding proteins (IGFBPs) in human breast cancer and in normal mammary epithelium. IGF1, hyperinsulinaemia and breast cancerA considerable literature has shown that insulin-like growth factors IGF1 and IGF1 1 can stimulate the growth of human breast cancer cell lines in vitro (summarized in Westley and May, 1994).The mitogenic effects of both IGF1 and IGF1 1 are thought to be mediated mainly by their binding to the IGF1 receptor, which is located mainly in the epithelial component of breast cancer (Ellis et al, 1994). Both IGFs are expressed in the stromal component suggesting that they mainly exert a paracrine effect on the epithelium (Singer et al, 1995) but in addition, circulating IGF1 may exert an endocrine effect on breast tissue.It is relevant that hyperinsulinaemia is associated with raised levels of IGF1 and in addition, insulin levels determine the

show abstract

Induction of mammary adenocarcinomas in metallothionein promoter‐human growth hormone transgenic mice

Törnell

Rymo

Isaksson

1991

Intl Journal of Cancer

View full text Add to dashboard Cite

To develop transgenic mice, a mouse metallothionein promoter-human growth hormone (Mt-hGH) gene fragment was injected into the pronucleus of C57BI x DBA/2J F2 one-cell embryos. Six founder animals grew larger (1.3-2.2 times) than littermate controls and had higher levels of hGH in plasma (4.6-279 mU/l). At 27-43 weeks of age, 3 of the 4 female transgenic founders developed malignant papillary adenocarcinomas of mammary origin. One of the male transgenic founders was successfully mated and 2 of 3 female transgenic offspring developed mammary tumors. Forty-two female mice with the same genetic background as the transgenic animals and older than 43 weeks served as controls. No palpable tumor was found in this group. Five of the control animals were killed and examined histologically, revealing only normal mammary tissue. Earlier studies have shown that GH is important for growth and development of the mammary gland. Our study suggests that markedly elevated endogenous levels of GH cause mammary carcinoma in a specific strain of transgenic mice. The present animal model might be useful for studying molecular mechanisms that are involved in the development of hormonally induced mammary tumors.

show abstract

Non-Lactogenic Effects of Growth Hormone on Growth and Insulin-Like Growth Factor-I Messenger Ribonucleic Acid of Rat Mammary Gland

Cited by 99 publications

References 15 publications

The effect of GH on estrogen receptor expression in the rat mammary gland

The effect of GH on estrogen receptor expression in the rat mammary gland

Breast cancer: further metabolic-endocrine risk markers?

Induction of mammary adenocarcinomas in metallothionein promoter‐human growth hormone transgenic mice

Contact Info

Product

Resources

About