Progesterone receptor in the mammary tissue of pregnant and lactating gilts and the effect of tamoxifen treatment during late gestation

Lin, Changjian; Buttle, H. L.

doi:10.1677/joe.0.1300251

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…PR mRNA was detected in tissues from nulliparous mice which decreased dramatically during pregnancy, became undetectable during lactation, and were once again detectable in glands from mice undergoing lactational involution (Shyamala et al 1990). The concentration of PR in gilt mammary gland was high at the onset of pregnancy and declined after 75 days until parturition, and the receptors were not identifiable at day 21 of lactation (Lin & Buttle 1991).…”

Section: Discussionmentioning

confidence: 98%

Expression and localisation of oestrogen and progesterone receptors in the bovine mammary gland during development, function and involution

Schams¹,

Kohlenberg²,

Amselgruber³

et al. 2003

Journal of Endocrinology

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It is now well established that oestrogen and progesterone are absolutely essential for mammary gland development. Lactation can be induced in non-pregnant animals by sex steroid hormone treatment. Most of the genomic actions of oestrogens are mediated by two oestrogen receptors (ER)-and ER , and for gestagens in ruminants by the progesterone receptor (PR). Our aim was the evaluation of mRNA expression and protein (localisation and Western blotting) during mammogenesis, lactogenesis, galactopoiesis (early, middle and late) and involution (8, 24, 28,(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108) h and 14-28 days after the end of milking) in the bovine mammary gland (total no. 53). During these stages, the mRNA was assessed by means of real-time RT-PCR (LightCycler). The protein for ER , ER and PR was localised by immunohistochemistry and Western blotting. The mRNA expression results indicated the existence of ER , ER and PR in bovine mammary gland. Both ER and PR are expressed in fg/µg total RNA range. The highest mRNA expression was found for ER and PR in the tissue of non-pregnant heifers, followed by a significant decrease to a lower level at the time of lactogenesis with low concentrations remaining during lactation and the first 4 weeks of involution. In contrast, the expression of ER was about 1000-fold lower (ag/µg total RNA) and showed no clear difference during the stages examined, with a significant increase only 2-4 weeks after the end of milking. Immunolocalisation for ER revealed a strong positive staining in nuclei of lactocytes in non-pregnant heifers, became undetectable during pregnancy, lactogenesis and lactation, and was again detectable 14-28 days after the end of milking. In contrast, PR was localised in the nuclei of epithelial cells in the mammary tissue of non-pregnant heifers, in primigravid animals, and during late lactation and involution. During lactogenesis, peak and mid lactation, fewer nuclei of epithelial cells were positive, but increased staining of the cytoplasm of epithelial cells was obvious. ER and ER protein was found in all mammary gland stages examined by Western blotting. In contrast to mRNA expression, the protein signal for ER was weaker in the tissue of non-pregnant heifers and during involution (4 weeks). ER protein showed a stronger signal (two isoform bands) in non-pregnant heifers and 4 weeks after the end of milking. This correlated with the mRNA expression data. Three isoforms of PR (A, B and C) were found by Western blotting in the tissue of non-pregnant heifers, but only isoform B remained during the following stages (lactogenesis, galactopoiesis and involution). In conclusion, the mRNA expression and protein data for ER and PR showed clear regulatory changes, suggesting involvement of these receptors in bovine mammary gland development and involution.

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Section: Discussionmentioning

confidence: 98%

Expression and localisation of oestrogen and progesterone receptors in the bovine mammary gland during development, function and involution

Schams¹,

Kohlenberg²,

Amselgruber³

et al. 2003

Journal of Endocrinology

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“…Early studies showed that the relative binding affinity of E2 for PR is less than 0.3% of progesterone (36). With a dissociation constant of 10 Ϫ9 M for progesterone binding, the estimated dissociation constant for E2 would be in the range of 10 Ϫ6 M. It is thus theoretically not possible for E2 at 10 Ϫ9 M to bind to PR significantly.…”

Section: Discussionmentioning

confidence: 99%

A Novel Antiestrogenic Mechanism in Progesterone Receptor-transfected Breast Cancer Cells

Zheng

Bay

et al. 2005

Journal of Biological Chemistry

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The expression of progesterone receptor (PR) is normally estrogen-dependent, and progesterone is only active in target cells following estrogen exposure. This study revealed that the effect of estrogen was markedly disrupted by estrogen-independent expression of PR. Ovarian steroid hormones estrogen and progesterone are essential for the normal growth and development of the breast. The two hormones also play critical roles in the regulation of breast cancer development. It has been established that estrogen stimulates the growth of breast cancer cells both in vivo and in vitro (1-3). Antiestrogens have been the front-line therapy for hormone-dependent breast cancers (4), which are estrogen receptor (ER) 1 -and progesterone receptor (PR)-positive. Nonetheless, antiestrogen-induced remissions are often followed by acquisition of antiestrogen resistance and ultimately disease relapse (5). The acquired resistance is mostly manifested by insensitivity to antiestrogens such as tamoxifen and increased ER activity (6). It has been shown that signaling via the epidermal growth factor receptor and HER-2/neu can activate both ER and the important ER coactivator AIB1 (7). Breast tumors with high levels of AIB1 and HER-2 may be resistant to tamoxifen because of an increase in its estrogen agonist activity. The development of strategies for the effective treatment of tamoxifen-resistant breast cancer is one of the main challenges for breast cancer research. Transfection of PR in estrogen receptor (ER)-Whereas it is established that estrogen stimulates the growth of breast cancer cells, the function of progesterone in breast cancer remains controversial. Progestins were found to stimulate growth, have no effect, or inhibit growth depending on the experimental conditions and the status of hormone receptors (8 -11). This controversy reflects our insufficient understanding of progesterone biology and has hampered effective applications of progestins or antiprogestins in breast cancer treatment.The controversies over the effect of progesterone in breast cancer are due to several complexities in the PR system. One of the complexities is that PR is an estrogen receptor-dependent gene product (12, 13), and the action of progesterone requires priming treatment of estrogen to induce PR. It is conceivable that the prior presence of estrogen may significantly confound assessment of the role of progesterone on growth and other cellular processes in breast cancer cells. On the other hand, the effects of progesterone also depend on a complex interaction between estrogen, progesterone, and their receptors. Studies have demonstrated the suppression of estrogen-stimulated ER activity by agonist-and antagonist-occupied PR (14 -15). However, ER can transmit signals received from the agonist-activated PR to the Src/p21 (ras)/Erk pathway (16), suggesting a synergistic interaction between the ER and PR.Our previous work has shown that estrogen-independent expression of PR by transfection in the ER-and PR-negative breast cancer cells MDA-MB-231, fac...

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“…Procedures for the assay of progesterone receptors in uterine tissue were similar to that described pre¬ viously for mammary tissue (Lin & Buttle, 1991). Briefly, powdered uterine tissue (0-5 g wet weight) was homogenized in 10 ml potassium phosphate buffer (10 mmol/1; pH 7-4) containing 30% (v/v) glycerol, 5 mmol monothioglycerol/1 and 1 mmol sodium azide/1.…”

Section: Assays Progesterone Receptor Assaymentioning

confidence: 99%

“…Aliquots (250 µ ) of the cytosol preparation were incubated in duplicate with 10 nmol [ H]progesterone/tube for 20 h in the presence or absence of a 100-fold molar excess of unlabelled progesterone. The rest of the assay pro¬ cedures were as described previously (Lin & Buttle, 1991). …”

Section: Assays Progesterone Receptor Assaymentioning

confidence: 99%

“…In this study, the effects of oestradiol benzoate and tamoxifen on the growth and the induction of pro¬ gesterone receptors in cytosolic extracts from the uterus and mammary gland were investigated in immature pigs so as to provide further information on the bio¬ logical effects of tamoxifen, and to investigate the reasons for the apparent failure of tamoxifen to affect mammary growth, differentiation and development of progesterone receptors when given to late-pregnant gilts (Lin & Buttle, 1991).…”

Section: Introductionmentioning

confidence: 99%

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Effect of oestradiol benzoate and tamoxifen on the growth of and induction of progesterone receptors in the uterus and mammary gland of immature pigs

Lin¹,

Buttle²

1991

Journal of Endocrinology

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Intramuscular injection of oestradiol benzoate (0.1, 1 or 10 micrograms/kg per day) and tamoxifen (0.1 or 1 mg/kg per day) to 6-week-old immature pigs for 7 days induced a dose-dependent increase in the wet weight of the uterus and in the total content of uterine DNA, RNA and protein. Both compounds also stimulated a dose-dependent increase in the concentration of progesterone receptors in uterine cytosolic extracts (in terms of either fmol/mg DNA or fmol/g uterus). The concurrent administration of tamoxifen with oestradiol benzoate provoked significant (P less than 0.05) increases in total uterine protein and in the concentration of progesterone receptors (P less than 0.01) compared with treatment with oestradiol benzoate alone. Hence tamoxifen is an oestrogen agonist in the uterus of immature pigs. The effects of oestradiol benzoate and tamoxifen on mammary growth in immature pigs were assessed by image analysis of mammary sections across the gland (in a ventro-dorsal direction through the teat). Oestradiol benzoate at 10 micrograms/kg per day stimulated a fourfold increase in mammary duct area (P less than 0.01), and tamoxifen, at doses of 0.1 or 1 mg/kg per day, stimulated a threefold increase (P less than 0.05). Tamoxifen partially inhibited (P less than 0.05) the effect of oestradiol benzoate. The concentration of progesterone receptors was found to be very heterogeneous in cytosol extracts of mammary tissue of immature pigs and independent of treatment with oestradiol benzoate and/or tamoxifen.

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Progesterone receptor in the mammary tissue of pregnant and lactating gilts and the effect of tamoxifen treatment during late gestation

Cited by 8 publications

References 26 publications

Expression and localisation of oestrogen and progesterone receptors in the bovine mammary gland during development, function and involution

Expression and localisation of oestrogen and progesterone receptors in the bovine mammary gland during development, function and involution

A Novel Antiestrogenic Mechanism in Progesterone Receptor-transfected Breast Cancer Cells

Effect of oestradiol benzoate and tamoxifen on the growth of and induction of progesterone receptors in the uterus and mammary gland of immature pigs

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