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[Endometrial nuclear progesterone receptors in infertile women]

[Article in Chinese]

Dai L, Shen H, Yu Y, Wang Y, Zuo W, Kan X.

Department of Pathology, People's Hospital, Beijing Medical University, Beijing 100044, China.

OBJECTIVE: To investigate the endometrial nuclear progesterone receptors (PgR) as well as its relationship with retarded endometrial development (RED) in infertile women. METHODS: The progesterone profile, endometrial nuclear progesterone receptors (PgR) and endometrial biopsies were studied by using (125)I radioimmunoassay and immunohistochemical technique in 53 infertile women during median luteal phase. When the endometrial dating lagged 2 days behind the dating as determined by luteinizing hormone (LH) surge, diagnosis of luteal phase defect (LPD) was made. According to progesterone profile and endometrial morphology, the patients were divided into three groups: normal, luteal phase defect (LPD) and pseudocorpus luteum insufficiency (PLI). RESULTS: During median luteal phase, RED were found in all of 24 cases with LPD and PLI, but PgR contents were different in them. Mean progesterone profile of 9 cases of PLI cycles was normal (60.2 nmol/L) but the endometrial nuclear PgR appeared to be prominently lower than in normal cycles during the median luteal phase (P < 0.01). Average progesterone level of 15 cases of LPD cycles were significantly lower (29.9 nmol/L) but endometrial nuclear PgR were similar to normal group (P > 0.05). CONCLUSION: Retarded endometrial development may have different causes. Measurement of endometrial nuclear PgR is of assistance in differential diagnosis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11866909&dopt=Abstract progesterone, progesterone cream



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Interrelationships among plasma progesterone concentrations, luteal anatomy and function, and placental ontogeny during gestation in a viviparous lizard (Niveoscincus metallicus: Scincidae).

Bennett EJ, Jones SM.

School of Zoology, University of Tasmania, GPO Box 252-05, Hobart, Tasmania 7001, Australia.

Plasma progesterone concentrations were measured at six stages of gestation in the viviparous lizard Niveoscincus metallicus. Anatomical and functional parameters of luteal activity were also investigated. The diameter of the corpus luteum (CL) decreased gradually though gestation, as did the diameter of the luteal cells. Major degenerative changes were observed in CLs post-partum. Plasma progesterone concentrations were basal both prior to, and just after, ovulation; a rapid increase occurred in early gestation. Plasma progesterone concentrations remained elevated until late gestation, but fell some 2 weeks before parturition. In vitro production of progesterone was greater in CLs in mid- than in late-gestation, and the addition of prostaglandin F(2alpha) to the incubation medium had no effect on progesterone production. Non-luteal ovarian tissue and adrenals produced progesterone, but at approximately one-tenth the rate of production by CLs. Temporal correlations between the plasma progesterone profile and stages of placental development were also assessed. The rise in plasma progesterone concentrations occurs before differentiation of the chorioallantoic placenta, but progesterone is still high when it degenerates. We conclude that the CLs are the major source of gestational progesterone in N. metallicus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11867290&dopt=Abstract progesterone, progesterone cream



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Progesterone induces cellular differentiation in MDA-MB-231 breast cancer cells transfected with progesterone receptor complementary DNA.

Lin VC, Jin R, Tan PH, Aw SE, Woon CT, Bay BH.

Departments of Clinical Research and Pathology, Singapore General Hospital, Singapore.

Progesterone is an important regulator of growth and differentiation in breast tissues. In this study, the effect of progesterone on cell differentiation was evaluated in the estrogen receptor-negative and progesterone receptor (PR)-negative MDA-MB-231 cell line which was transfected with PR-complementary DNA. Morphological changes were analyzed at the ultrastructural level by scanning and transmission electron microscopy. Progesterone-treated PR-transfected cells exhibited a more protracted and well spread morphology with an increase in organelles such as mitochondria and rough endoplasmic reticulum as compared to the rounded form of control vehicle (0.1% ethanol)-treated PR-transfected cells. Vehicle and progesterone-treated MDA-MB-231 cells transfected with the pSG5 plasmid (transfection control cells) had similar rounded morphology as control vehicle-treated PR-transfected cells. Immunofluorescence staining revealed that expression of E-cadherin, a differentiation marker, was more prominent in progesterone-treated cells. Expression of keratin and vimentin but not beta-catenin was up-regulated in progesterone treated cells when evaluated by immunoblotting. As signal transducers and activators of transcription (STAT) molecules have been implicated in mammary differentiation, we analyzed the expression of Stat 1, 3, 5a, and 5b proteins and found a significant up-regulation of the Stat 5b protein in progesterone-treated cells. We have provided in vitro evidence of the close association of PR with differentiation in breast cancer. It is likely that the Stat 5b protein may play a major role in progesterone-induced differentiation in breast cancer cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12759236&dopt=Abstract progesterone, progesterone cream



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Regulation of endometrial endothelial cell proliferation by oestrogen and progesterone in the ovariectomized mouse.

Heryanto B, Rogers PA.

Centre for Women's Health Research, Monash University Department of Obstetrics and Gynaecology, Monash Medical Centre, 246 Clayton Rd, Clayton, Victoria 3168, Australia.

Although the endometrial epithelial and stromal cell response to oestrogen and progesterone is well characterized, relatively little is known about the endothelial cell response. The aim of this study was to investigate the time course of endometrial endothelial cell proliferation in response to a specific regimen of oestrogen and progesterone, and to compare it with the stromal and epithelial cell response in mouse endometrium. Adult female mice were ovariectomized to induce endometrial regression. After 7 days, hormonal treatments were given according to the following regimen: days 1-3: 100 ng oestradiol; days 4-6: 10 ng oestradiol and 500 microg progesterone; and day 7: 100 ng oestradiol and 500 microg progesterone. On each day of hormonal treatment, mice (n = 5) were injected with bromodeoxyuridine and perfusion fixed 4 h later with buffered formalin. Proliferating endometrial cells were detected by monoclonal antibody against bromodeoxyuridine, and endothelial cells were detected by antibody to CD31. At day 7 after ovariectomy few proliferating cells were found in the endometrium. After 1 day of oestrogen treatment, significant proliferation was detected in the endothelial cells (0.0% versus 16.1 +/- 1.2%, P < 0.001). In contrast to the rapid response of the vasculature, glandular epithelial proliferation increased only after 2 days of oestrogen treatment (7.6 +/-1.3% versus 18.8 +/- 2.4%, P < 0.05). Progesterone with low dose oestrogen treatment tended to reduce epithelial and endothelial cell proliferation compared with the effect of high dose oestradiol alone. A combination of progesterone with high dose oestrogen induced higher rates of endothelial cell proliferation than did any other treatment (20.8 +/- 3.2%). These results demonstrate that oestrogen induces rapid proliferation of endometrial endothelial cells, indicating that vascular growth apparently precedes endometrial tissue remodelling. These data also demonstrate that the proliferative response of endometrial endothelial cells to oestrogen and progesterone is different from that of either epithelial or stromal cells.

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Modulation of nerve growth factor in peripheral organs by estrogen and progesterone.

Bjorling DE, Beckman M, Clayton MK, Wang ZY.

Department of Surgical Sciences, School of Veterinary Medicine, The University of Wisconsin, 2015 Linden Drive West, Madison, WI 53706, USA. bjorlind svm.vetmed.wisc.edu

Nerve growth factor (NGF) synthesized in peripheral organs plays a critical role in the development and maintenance of the nervous system and also participates in processing nociceptive stimuli. Previous studies suggest that reproductive hormones may regulate the expression of NGF. Ovariectomies were performed on female mice, and mice were killed 24 h after hormone replacement to evaluate the effects of estrogen and progesterone on NGF in peripheral organs, specifically the uterus, bladder, heart, and salivary gland. Sham-operated intact mice and untreated ovariectomized mice served as controls. Immunohistochemistry demonstrated the presence of NGF, estrogen receptor-alpha, estrogen receptor-beta, and progesterone receptors in these organs. Ovariectomy caused a significant decrease in NGF protein content in the uterus, and short term treatment of ovariectomized mice with estrogen and/or progesterone increased uterine NGF mRNA and restored NGF protein to concentrations similar to intact control mice. Ovariectomy did not affect NGF protein concentrations in the salivary gland, but treatment of ovariectomized mice with estrogen alone or in conjunction with progesterone stimulated concentrations of NGF protein that exceeded those observed in intact control or ovariectomized, untreated mice. NGF mRNA was increased in salivary glands from ovariectomized mice treated with progesterone alone or in combination with estrogen relative to other groups. NGF protein content of the hearts of ovariectomized mice treated with estrogen alone or in conjunction with progesterone was increased relative to intact controls and ovariectomized, untreated mice, but neither ovariectomy or hormone replacement affected NGF mRNA content in the heart. NGF protein content of the bladder was unaffected by ovariectomy or hormone treatment, and bladder NGF mRNA was unaffected by ovariectomy or hormone treatment. Collectively, these results indicate that reproductive hormones have the capacity to regulate NGF message and protein in a manner that varies among organs. Fluctuations in the expression of NGF, in conjunction with other factors, may help to explain gender differences in pain sensation and inflammatory response.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11882380&dopt=Abstract progesterone, progesterone cream



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Transcriptional regulation of the mouse steroid 5alpha-reductase type II gene by progesterone in brain.

Matsui D, Sakari M, Sato T, Murayama A, Takada I, Kim M, Takeyama K, Kato S.

Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan.

The steroid 5alpha-reductase (5alpha-R) plays an important physiological role in the conversion of steroid hormones such as androgen and progesterone to their 5alpha-reduced derivatives. 5alpha-R type II (5alpha-R2), one of two 5alpha-R isoforms, is thought to be a key enzyme in the generation of neuroactive steroids in the brain, particularly allopregnanolone (AP), via the production of its precursor dihydroprogesterone from progesterone. In the present study, we investigated possible regulatory mechanisms of 5alpha-R2 gene expression by steroid hormones in the female mouse brain. We first cloned mouse 5alpha-R2 (m5alpha-R2) cDNA by degenerate PCR, and found that progesterone induced 5alpha-R2 gene expression to levels detectable by in situ hybridization in female mouse brains. Functional analysis of the m5alpha-R2 gene promoter by a transient expression assay with human progesterone receptor (PR) and androgen receptor (AR) expression vectors identified a progesterone and androgen regulatory element (m5alpha-R2 PRE/ARE). Results of an electrophoretic mobility shift assay revealed that both PR and AR homodimers bound directly to m5alpha-R2 PRE/ARE sequence. These findings suggest that the gene expression of m5alpha-R2 is transcriptionally regulated by progesterone in female brains.

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Luteal activity at the onset of a timed insemination protocol affects reproductive outcome in early postpartum dairy cows.

Murugavel K, Yaniz JL, Santolaria P, Lopez-Bejar M, Lopez-Gatius F.

Department of Animal Production, University of Lleida, Lleida, Spain.

This study was designed to compare two timed insemination protocols, in which progesterone, GnRH and PGF2alpha were combined, with the Ovsynch protocol in presynchronized, early postpartum dairy cows. Reproductive performance was also evaluated according to whether cows showed high or low plasma progesterone concentration, at the onset of treatment. One hundred and six early postpartum dairy cows were presynchronized with two cloprostenol treatments given 14 days apart, and then assigned to one of the three treatment groups. Treatments for the synchronization of estrus in all three groups started 7 days after the second cloprostenol injection, which was considered Day 0 of the actual treatment regime. Cows in the control group (Ovsynch, n=30) were treated with GnRH on Day 0, PGF2alpha on Day 7, and were given a second dose of GnRH 32 h later. Cows in group PRID (n=45) were fitted with a progesterone releasing intravaginal device (PRID) for 9 days, and were given GnRH at the time of PRID insertion and PGF2alpha on Day 7. In group PRID/GnRH (n=31), cows received the same treatment as in the PRID group, but were given an additional GnRH injection 36 h after PRID removal. Cows were inseminated 16-20 h after the administration of the second GnRH dose in the Ovsynch group, and 56 h after PRID removal in the PRID and PRID/GnRH groups. Ovulation rate was determined on Day 11 postinsemination by detecting the presence of a corpus luteum in the ovaries. Lactation number, milk production, body condition at the onset of treatment and treatment regime were included as potential factors influencing ovulation and pregnancy after synchronization. Logistic regression analysis for cows with high and low progesterone concentration on treatment Day 0 revealed that none of the factors included in the models, except the interaction between progesterone and treatment regime, influenced the risk of ovulation and pregnancy significantly. In cows with high progesterone concentration at treatment onset, Ovsynch treatment resulted in a significantly improved pregnancy rate over values obtained following PRID or PRID/GnRH treatment. In cows with low progesterone concentration, PRID or PRID/GnRH treatment led to markedly increased ovulation and pregnancy rates with respect to Ovsynch treatment. These findings suggest the importance of establishing ovarian status in early postpartum dairy cows before starting a timed AI protocol, in terms of luteal activity assessed by blood progesterone.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12763171&dopt=Abstract progesterone, progesterone cream