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R.B. · 07-25-2006, 01:46 PM

I have referred to this previously and just refound where I filed it.

It is interesting in that it suggest that local levels of estradiol were higher in the breast in correlation with higher progesterone.

As this increase was not seen in abdominal tissue this suggest it is being locally produced?

Progesterone is produced in the period post ovulation presumably preparing the body for attachment and growth of the egg.

Have the implications of progesterone in HER2 been explored?

What about ER beta receptors.? "and life span via a receptor (ERbeta)-mediated pathway" What are the implications for a life span mediator.

This is very much beyond beyond my very very very limited BC mechanism knowledge.

I just post it in case it of use to somebody else.

RB

http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

1: J Endocrinol. 2005 Oct;187(1):103-8. Links
Increased extracellular local levels of estradiol in normal breast in vivo during the luteal phase of the menstrual cycle.
• Dabrosin C.
Division of Gynaecologic Oncology, Faculty of Health Sciences, University Hospital, SE-581 85 Linkoping, Sweden. chada@ibk.liu.se
Estrogen exposure is a major risk factor for breast cancer. Tissue estrogen originates from the ovaries but a significant portion is also produced by enzyme activity locally in the breast itself. How these enzymes are regulated is not fully understood. The extracellular space, where the metabolic exchange and cell interactions take place, reflects the environment that surrounds the epithelium but there has been no previous study of hormone concentrations in this compartment. In the present study microdialysis was used to measure extracellular estrogen concentrations in breast tissue and abdominal subcutaneous fat in 12 healthy women in vivo. It was found that women with high plasma progesterone levels had significant increased levels of estradiol in breast tissue compared with fat tissue (breast tissue 168+/-6 pM; subcutaneous fat, 154+/-5 pM; P<0.05), whereas women with low plasma progesterone exhibited no difference. Moreover, there was a significant correlation between local breast tissue estradiol and plasma progesterone levels (r=0.709, P<0.01). There was no difference in estrone sulphate in breast and fat tissue regardless of progesterone levels. Estrone was not detectable. The results in this study suggest that progesterone may be one regulator in the local conversion of estrogen precursors into potent estradiol in normal breast tissue.
PMID: 16214945 [PubMed - indexed for MEDLINE]

1: J Histochem Cytochem. 1999 Oct;47(10):1323-30.Click here to read Links
Murine progesterone receptor expression in proliferating mammary epithelial cells during normal pubertal development and adult estrous cycle. Association with eralpha and erbeta status.

* Zeps N,
* Bentel JM,
* Papadimitriou JM,
* Dawkins HJ.

Urological Research Centre and Clinic, Department of Surgery, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, WA, Australia.

The ovarian steroids estrogen and progesterone are important in directing the normal growth and development of the mouse mammary gland. Previously, we have demonstrated that the majority of proliferating mammary epithelial cells do not express estrogen receptor-alpha (ERalpha). In this study we examined the relationship between progesterone receptor (PR) expression and proliferation in mammary epithelial cells using simultaneous immunohistochemistry for progesterone receptor (PR) and tritiated thymidine [(3)H]-Tdr) autoradiography. Results showed that the majority (>80%) of mammary epithelial cells labeled with [(3)H]-Tdr were PR-positive in the terminal end buds (TEBs) of pubertal mice and the ducts of pubertal and adult mice. Whereas the majority of mammary epithelial cells were also PR-positive, the basal cell population, which comprises the minority of mammary epithelial cells in the mammary ducts, was predominantly PR-negative. Nevertheless, the PR-positive phenotype remained the major proliferating cell type in the basal population. These findings suggest that the progesterone signaling pathway is involved in the proliferation of basal cell populations, potentially directing formation of tertiary side branching during pubertal development and alveolar bud formation in adult glands. A proportion of the basal cells exhibited weak expression of ERbeta, suggesting that the role of ERbeta in mediating normal estrogen-induced responses should be further studied. (J Histochem Cytochem: 47:1323-1330, 1999)

PMID: 10490461 [PubMed - indexed for MEDLINE]

1: Endocrinology. 2000 May;141(5):1711-7.Click here to read Links
Expression of estrogen receptor alpha and beta in the rhesus monkey corpus luteum during the menstrual cycle: regulation by luteinizing hormone and progesterone.

* Duffy DM,
* Chaffin CL,
* Stouffer RL.

Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006, USA. duffyd@ohsu.edu

There are conflicting reports on the presence or absence of estrogen receptor (ER) in the primate corpus luteum, and the discovery of a second type of estrogen receptor, ERbeta, adds an additional level of complexity. To reevaluate ER expression in the primate luteal tissue, we used semiquantitative RT-PCR based assays and Western blotting to assess ERalpha and beta messenger RNA (mRNA) and protein levels in corpora lutea (n = 3/stage) obtained from adult female rhesus monkeys at early (days 3-5), mid (days 6-8), mid-late (days 10-12), and late (days 14-16) luteal phase of the natural menstrual cycle. ERalpha mRNA levels did not vary across the stages of the luteal phase, and ERalpha protein was not consistently detected in luteal tissues. However, ERbeta mRNA and protein levels were detectable in early and mid luteal phases and increased (P < 0.05) to peak levels at mid-late luteal phase before declining by late luteal phase. To determine if ERbeta mRNA expression in the corpus luteum is regulated by LH, monkeys received the GnRH antagonist antide either alone or with 3 daily injections of LH to simulate pulsatile LH release. Treatment with antide alone or concomitant LH administration did not alter luteal ERbeta mRNA levels. When monkeys also received the 3beta-hydroxysteroid dehydrogenase inhibitor trilostane to reduce luteal progesterone production, luteal ERbeta mRNA levels were 3-fold higher (P < 0.05) than in monkeys receiving antide + LH only. Replacement of progestin activity with R5020 reduced luteal ERbeta mRNA levels to those seen in animals receiving antide + LH. Thus, there is dynamic ERbeta expression in the primate corpus luteum during the menstrual cycle, consistent with a role for estrogen in the regulation of primate luteal function and life span via a receptor (ERbeta)-mediated pathway. Increased ERbeta expression in the progestin-depleted corpus luteum during LH exposure suggests that the relative progestin deprivation experienced by the corpus luteum between LH pulses may enhance luteal sensitivity to estrogens during the late luteal phase of the menstrual cycle.

PMID: 10803581 [PubMed - indexed for MEDLINE]

07-25-2006, 01:46 PM	#1
R.B. Senior Member Join Date: Mar 2006 Posts: 1,843	A role for progesterone I have referred to this previously and just refound where I filed it. It is interesting in that it suggest that local levels of estradiol were higher in the breast in correlation with higher progesterone. As this increase was not seen in abdominal tissue this suggest it is being locally produced? Progesterone is produced in the period post ovulation presumably preparing the body for attachment and growth of the egg. Have the implications of progesterone in HER2 been explored? What about ER beta receptors.? "and life span via a receptor (ERbeta)-mediated pathway" What are the implications for a life span mediator. This is very much beyond beyond my very very very limited BC mechanism knowledge. I just post it in case it of use to somebody else. RB http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum 1: J Endocrinol. 2005 Oct;187(1):103-8. Links Increased extracellular local levels of estradiol in normal breast in vivo during the luteal phase of the menstrual cycle. • Dabrosin C. Division of Gynaecologic Oncology, Faculty of Health Sciences, University Hospital, SE-581 85 Linkoping, Sweden. chada@ibk.liu.se Estrogen exposure is a major risk factor for breast cancer. Tissue estrogen originates from the ovaries but a significant portion is also produced by enzyme activity locally in the breast itself. How these enzymes are regulated is not fully understood. The extracellular space, where the metabolic exchange and cell interactions take place, reflects the environment that surrounds the epithelium but there has been no previous study of hormone concentrations in this compartment. In the present study microdialysis was used to measure extracellular estrogen concentrations in breast tissue and abdominal subcutaneous fat in 12 healthy women in vivo. It was found that women with high plasma progesterone levels had significant increased levels of estradiol in breast tissue compared with fat tissue (breast tissue 168+/-6 pM; subcutaneous fat, 154+/-5 pM; P<0.05), whereas women with low plasma progesterone exhibited no difference. Moreover, there was a significant correlation between local breast tissue estradiol and plasma progesterone levels (r=0.709, P<0.01). There was no difference in estrone sulphate in breast and fat tissue regardless of progesterone levels. Estrone was not detectable. The results in this study suggest that progesterone may be one regulator in the local conversion of estrogen precursors into potent estradiol in normal breast tissue. PMID: 16214945 [PubMed - indexed for MEDLINE] 1: J Histochem Cytochem. 1999 Oct;47(10):1323-30.Click here to read Links Murine progesterone receptor expression in proliferating mammary epithelial cells during normal pubertal development and adult estrous cycle. Association with eralpha and erbeta status. * Zeps N, * Bentel JM, * Papadimitriou JM, * Dawkins HJ. Urological Research Centre and Clinic, Department of Surgery, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, WA, Australia. The ovarian steroids estrogen and progesterone are important in directing the normal growth and development of the mouse mammary gland. Previously, we have demonstrated that the majority of proliferating mammary epithelial cells do not express estrogen receptor-alpha (ERalpha). In this study we examined the relationship between progesterone receptor (PR) expression and proliferation in mammary epithelial cells using simultaneous immunohistochemistry for progesterone receptor (PR) and tritiated thymidine [(3)H]-Tdr) autoradiography. Results showed that the majority (>80%) of mammary epithelial cells labeled with [(3)H]-Tdr were PR-positive in the terminal end buds (TEBs) of pubertal mice and the ducts of pubertal and adult mice. Whereas the majority of mammary epithelial cells were also PR-positive, the basal cell population, which comprises the minority of mammary epithelial cells in the mammary ducts, was predominantly PR-negative. Nevertheless, the PR-positive phenotype remained the major proliferating cell type in the basal population. These findings suggest that the progesterone signaling pathway is involved in the proliferation of basal cell populations, potentially directing formation of tertiary side branching during pubertal development and alveolar bud formation in adult glands. A proportion of the basal cells exhibited weak expression of ERbeta, suggesting that the role of ERbeta in mediating normal estrogen-induced responses should be further studied. (J Histochem Cytochem: 47:1323-1330, 1999) PMID: 10490461 [PubMed - indexed for MEDLINE] 1: Endocrinology. 2000 May;141(5):1711-7.Click here to read Links Expression of estrogen receptor alpha and beta in the rhesus monkey corpus luteum during the menstrual cycle: regulation by luteinizing hormone and progesterone. * Duffy DM, * Chaffin CL, * Stouffer RL. Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006, USA. duffyd@ohsu.edu There are conflicting reports on the presence or absence of estrogen receptor (ER) in the primate corpus luteum, and the discovery of a second type of estrogen receptor, ERbeta, adds an additional level of complexity. To reevaluate ER expression in the primate luteal tissue, we used semiquantitative RT-PCR based assays and Western blotting to assess ERalpha and beta messenger RNA (mRNA) and protein levels in corpora lutea (n = 3/stage) obtained from adult female rhesus monkeys at early (days 3-5), mid (days 6-8), mid-late (days 10-12), and late (days 14-16) luteal phase of the natural menstrual cycle. ERalpha mRNA levels did not vary across the stages of the luteal phase, and ERalpha protein was not consistently detected in luteal tissues. However, ERbeta mRNA and protein levels were detectable in early and mid luteal phases and increased (P < 0.05) to peak levels at mid-late luteal phase before declining by late luteal phase. To determine if ERbeta mRNA expression in the corpus luteum is regulated by LH, monkeys received the GnRH antagonist antide either alone or with 3 daily injections of LH to simulate pulsatile LH release. Treatment with antide alone or concomitant LH administration did not alter luteal ERbeta mRNA levels. When monkeys also received the 3beta-hydroxysteroid dehydrogenase inhibitor trilostane to reduce luteal progesterone production, luteal ERbeta mRNA levels were 3-fold higher (P < 0.05) than in monkeys receiving antide + LH only. Replacement of progestin activity with R5020 reduced luteal ERbeta mRNA levels to those seen in animals receiving antide + LH. Thus, there is dynamic ERbeta expression in the primate corpus luteum during the menstrual cycle, consistent with a role for estrogen in the regulation of primate luteal function and life span via a receptor (ERbeta)-mediated pathway. Increased ERbeta expression in the progestin-depleted corpus luteum during LH exposure suggests that the relative progestin deprivation experienced by the corpus luteum between LH pulses may enhance luteal sensitivity to estrogens during the late luteal phase of the menstrual cycle. PMID: 10803581 [PubMed - indexed for MEDLINE]