The differences in neuroprotective efficacy of progesterone and medroxyprogesterone acetate correlate with their effects on brain-derived neurotrophic factor expression.

Whereas hormone therapy is used for the treatment of menopausal symptoms, its efficacy in helping reduce the risk of other diseases such as Alzheimer's disease has been questioned in view of the results of recent clinical trials that appeared inconsistent with numerous basic research studies that supported the beneficial effects of hormones. One possible explanation of this discrepancy may lie in the choice of hormone used. For example, we and others found that progesterone is neuroprotective whereas medroxyprogesterone acetate (MPA), the synthetic progestin used in hormone therapy, is not.

The RANKL signaling axis is sufficient to elicit ductal side-branching and alveologenesis in the mammary gland of the virgin mouse.

Receptor of Activated NF-kappaB Ligand (RANKL) is implicated as one of a number of effector molecules that mediate progesterone and prolactin signaling in the murine mammary epithelium. Using a mouse transgenic approach, we demonstrate that installation of the RANKL signaling axis into the mammary epithelium results in precocious ductal side-branching and alveologenesis in the virgin animal. These morphological changes occur due to RANKL-induced mammary epithelial proliferation, which is accompanied by increases in expression of activated NF-kB and cyclin D1.

Inherited thrombophilia and preeclampsia within a multicenter cohort: the Montreal Preeclampsia Study.

Objective: We sought to evaluate the association between inherited thrombophilia and preeclampsia.

Study Design: From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia and selected 443 control subjects who did not have preeclampsia or nonproteinuric gestational hypertension. Blood samples were tested for DNA polymorphisms affecting thrombophilia (factor V Leiden mutation, prothrombin G20210A mutation, methylenetetrahydrofolate reductase C677T polymorphism), homocysteine, and folate levels, and placentae underwent pathological evaluation.

beta-catenin mediates glandular formation and dysregulation of beta-catenin induces hyperplasia formation in the murine uterus.

Endometrioid adenocarcinoma is the most frequent form of endometrial cancer, usually developing in pre- and peri-menopausal women. beta-catenin abnormalities are common in endometrioid type endometrial carcinomas with squamous differentiation. To investigate the role of beta-catenin (Ctnnb1) in uterine development and tumorigenesis, mice were generated which expressed a dominant stabilized beta-catenin or had beta-catenin conditionally ablated in the uterus by crossing the PR(Cre) mouse with the Ctnnb1(f(ex3)/+) mouse or Ctnnb1(f/f) mouse, respectively.

Transcriptional response of the murine mammary gland to acute progesterone exposure.

Our mechanistic understanding of progesterone's involvement in murine mammary morphogenesis and tumorigenesis is dependent on defining effector pathways responsible for transducing the progesterone signal into a morphogenetic response. Toward this goal, microarray methods were applied to the murine mammary gland to identify novel downstream gene targets of progesterone. Consistent with a tissue undergoing epithelial expansion, mining of the progesterone-responsive transcriptome revealed the up-regulation of functional gene classes involved in epithelial proliferation and survival.

Conditional loss of uterine Pten unfailingly and rapidly induces endometrial cancer in mice.

Etiology of endometrial cancer (EMC) is not fully understood. Animal models with rapidly and spontaneously developing EMC will help explore mechanisms of cancer initiation and progression. Pten(+/-) mice are currently being used as a model to study EMC.

If-then contingencies and the differential effects of the availability of an attractive alternative on relationship maintenance for men and women.

In 7 experiments, the causal effects of the availability of an attractive alternative (AA) relationship partner on current relationship thoughts and intentions were tested using confederates, mental simulations, and virtual reality. Men behaved consistent with traditional relationship-commitment theories, showing decreased willingness to tolerate their partner's transgressions after the availability of an AA was made salient. However, consistent with a motivated cognition approach to commitment and work on relational self-construals, women increased their tolerance when presented with the relationship threat of an alternative.

Gap junction communication between uterine stromal cells plays a critical role in pregnancy-associated neovascularization and embryo survival.

In the uterus, the formation of new maternal blood vessels in the stromal compartment at the time of embryonic implantation is critical for the establishment and maintenance of pregnancy. Although uterine angiogenesis is known to be influenced by the steroid hormones estrogen (E) and progesterone (P), the underlying molecular pathways remain poorly understood. Here, we report that the expression of connexin 43 (Cx43), a major gap junction protein, is markedly enhanced in response to E in uterine stromal cells surrounding the implanted embryo during the early phases of pregnancy.

Isolation and partial characterization of Bacillus subtilis ME488 for suppression of soilborne pathogens of cucumber and pepper.

Environmentally friendly control measures are needed for suppression of soilborne pathogens of vegetable crops in the Republic of Korea. In vitro challenge assays were used to screen approximately 500 bacterial isolates from 20 Korean greenhouse soils for inhibition of diverse plant pathogens. One isolate, Bacillus subtilis ME488, suppressed the growth of 39 of 42 plant pathogens tested.

Steroid receptor coactivator 2: an essential coregulator of progestin-induced uterine and mammary morphogenesis.

The importance of the progesterone receptor (PR) in transducing the progestin signal is firmly established in female reproductive and mammary gland biology; however, the coregulators preferentially recruited by PR in these systems have yet to be comprehensively investigated. Using an innovative genetic approach, which ablates gene function specifically in murine cell-lineages that express PR, steroid receptor coactivator 2 (SRC-2, also known as TIF-2 or GRIP-1) was shown to exert potent coregulator properties in progestin-dependent responses in the uterus and mammary gland. Uterine cells positive for PR (but devoid of SRC-2) led to an early block in embryo implantation, a phenotype not shared by knockouts for SRC-1 or SRC-3.

Health visiting and community matrons: progress in partnership.

Since primary care services face their biggest challenges in the reorganisation of the NHS, a major theme for future service delivery is the effective management of clients with long-term conditions. Nationally, PCTs are committed to preparing experienced, senior nurses as community matrons, who will lead integrated health and social care for people with multiple long-term conditions and reduce hospital admissions. This paper discusses how health visitors can influence and support the development of local long-term condition services and the importance of health visitors working with community matrons to share their experiences and skills for the benefit of both patients and professionals.

In vivo analysis of progesterone receptor action in the uterus during embryo implantation.

In order for a successful pregnancy to occur, the embryo must attach to the luminal epithelial cells and invade into the stroma. Then, the surrounding stromal cells need to undergo decidualization in order to establish the vasculature necessary for survival of the embryo. These events in early pregnancy are tightly regulated by the steroid hormones, estrogen (E2) and progesterone (P4), through their cognate receptors, the estrogen receptor (ER) and the progesterone receptor (PR), respectively.

Bone growth and turnover in progesterone receptor knockout mice.

The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and microcomputed tomography analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 wk of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR.

Steroid receptor coactivator 2 is required for female fertility and mammary morphogenesis: insights from the mouse, relevance to the human.

Although the importance of the progesterone receptor (PR) to female reproductive and mammary gland biology is firmly established, the coregulators selectively co-opted by PR in these systems have not been clearly delineated. A selective gene-knockout approach applied to the mouse, which abrogates gene function only in cell types that express PR, recently disclosed steroid receptor coactivator 2 (SRC-2, also known as TIF-2 or GRIP-1) to be an indispensable coregulator for uterine and mammary gland responses that require progesterone. Uterine cells positive for PR (but devoid of SRC-2) were found to be incapable of facilitating embryo implantation, a necessary first step toward the establishment of the materno-fetal interface.

Peroxisome proliferator-activated receptor gamma is a target of progesterone regulation in the preovulatory follicles and controls ovulation in mice.

The progesterone receptor (PR) plays a critical role during ovulation. Mice lacking the PR gene are anovulatory due to a failure in the rupture of the preovulatory follicles. The pathways that operate downstream of PR to control ovulation are poorly understood.

Maternal heparin-binding-EGF deficiency limits pregnancy success in mice.

An intimate discourse between the blastocyst and uterus is essential for successful implantation. However, the molecular basis of this interaction is not clearly understood. Exploiting genomic Hbegf mutant mice, we show here that maternal deficiency of heparin-binding EGF-like growth factor (HB-EGF) defers on-time implantation, leading to compromised pregnancy outcome.

Targeting reverse tetracycline-dependent transactivator to murine mammary epithelial cells that express the progesterone receptor.

Through an established gene-targeting strategy, reverse tetracycline-dependent transactivator (rtTA) was targeted downstream of the murine progesterone receptor (PR) promoter. Mice were generated in which one (PR(+/rtTA)) or both (PR(rtTA/rtTA)) PR alleles harbor the rtTA insertion. The PR(+/rtTA) and PR(rtTA/rtTA) knockins exhibit phenotypes identical to the normal and the progesterone receptor knockout mouse, respectively.

A repressive role for prohibitin in estrogen signaling.

Nuclear receptor-mediated gene expression is regulated by corepressors and coactivators. In this study we demonstrate that prohibitin (PHB), a potential tumor suppressor, functions as a potent transcriptional corepressor for estrogen receptor alpha (ERalpha). Overexpression of PHB inhibits ERalpha transcriptional activity, whereas depletion of endogenous PHB increases the expression of ERalpha target genes in MCF-7 breast cancer cells.

The pattern of beta-catenin responsiveness within the mammary gland is regulated by progesterone receptor.

Experiments involving beta-catenin loss- and gain-of-function in the mammary gland have decisively demonstrated the role of this protein in normal alveologenesis. However, the relationship between hormonal and beta-catenin signaling has not been investigated. In this study, we demonstrate that activated beta-catenin rescues alveologenesis in progesterone receptor (PR; Pgr)-null mice during pregnancy.

COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity.

Progesterone and estrogen are critical regulators of uterine receptivity. To facilitate uterine remodeling for embryo attachment, estrogen activity in the uterine epithelia is attenuated by progesterone; however, the molecular mechanism by which this occurs is poorly defined. COUP-TFII (chicken ovalbumin upstream promoter transcription factor II; also known as NR2F2), a member of the nuclear receptor superfamily, is highly expressed in the uterine stroma and its expression is regulated by the progesterone-Indian hedgehog-Patched signaling axis that emanates from the epithelium.

Mouse models of implantation.

The process of implantation, necessary for nearly all viviparous birth, consists of tightly regulated reactions including apposition of the blastocyst, attachment to the uterine epithelium and decidualization of the uterine stroma. In order for implantation to be successful, a reciprocal interaction between an implantation competent blastocyst and receptive uterus must be achieved. A more thorough understanding of the molecular mechanisms that regulate uterine receptivity and implantation is of clinical relevance to correct implantation failure and improve pregnancy rates.

The p160 steroid receptor coactivator 2, SRC-2, regulates murine endometrial function and regulates progesterone-independent and -dependent gene expression.

The role of the p160 steroid receptor coactivator 2 (SRC-2) in the regulation of uterine function and progesterone (P4) signaling was investigated by determining the expression pattern of SRC-2 in the murine uterus during pregnancy and the impact of SRC-2 ablation on uterine function and global uterine gene expression in response to progesterone. SRC-2 is expressed in the endometrial luminal and glandular epithelium from pregnancy d 0.5.

Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of Msx2.

Branching morphogenesis within the peripubertal mouse mammary gland is directed by progesterone (P). A role for the homeobox-containing transcription factor, Msx2, during branching morphogenesis is suggested from its ontogenic expression profile and hormonal regulation. Herein, we define the spatio-temporal control of Msx2 expression, the regulation of its expression by P and its direct role in ductal branching morphogenesis.

Bmp2 is critical for the murine uterine decidual response.

The process of implantation, necessary for all viviparous birth, consists of tightly regulated events, including apposition of the blastocyst, attachment to the uterine lumen, and differentiation of the uterine stroma. In rodents and primates the uterine stroma undergoes a process called decidualization. Decidualization, the process by which the uterine endometrial stroma proliferates and differentiates into large epithelioid decidual cells, is critical to the establishment of fetal-maternal communication and the progression of implantation.

Progesterone-action in the murine uterus and mammary gland requires steroid receptor coactivator 2: relevance to the human.

The importance of the progesterone receptor (PR) in female reproductive and mammary gland biology is well recognized; however, the coregulators selectively enlisted by PR have yet to be comprehensively defined in vivo. To evaluate the involvement of steroid receptor coactivator (SRC)/p160 family members in these physiological systems, a mouse model (PRCre/+SRC-2flox/flox) was generated in which SRC-2 function was ablated specifically in cell-types that express the PR. Although PRCre/+SRC-2flox/flox ovarian activity was normal, uterine function was severely compromised.