Progesterone and progestin agonists are potent steroid hormones. There are at least three major types of progesterone receptor (PR) families that interact with and respond to progesterone or progestin ligands. These receptors include ligand-activated transcription factor isoforms (PR-A and PR-B) encoded by the PGR gene, often termed classical or nuclear progesterone receptor (nPR), membrane-spanning progesterone receptor membrane component proteins known as PGRMC1/2, and a large family of progestin/adipoQreceptors or PAQRs (also called membrane PRs or mPRs).
View Article and Find Full Text PDFOvarian cancer (OC) represents a collection of rare but lethal gynecologic cancers where the difficulty of early detection due to an often-subtle range of abdominal symptoms contributes to high fatality rates. With the exception of BRCA1/2 mutation carriers, OC most often manifests as a post-menopausal disease, a time in which the ovaries regress and circulating reproductive hormones diminish. Progesterone is thought to be a "protective" hormone that counters the proliferative actions of estrogen, as can be observed in the uterus or breast.
View Article and Find Full Text PDFContext: The ability of ovarian steroids to modify ovarian cancer (OC) risk remains controversial. Progesterone is considered to be protective; recent studies indicate no effect or enhanced OC risk. Knowledge of progesterone receptor (PR) signaling during altered physiology that typifies OC development is limited.
View Article and Find Full Text PDFJ Steroid Biochem Mol Biol
February 2018
Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR).
View Article and Find Full Text PDFThe mechanism(s) underlying photorefractoriness in temperate zone seasonally breeding birds remains undetermined. Our recent findings reveal a link between the upregulation of GABA receptors (GABARs) in the premammillary nucleus (PMM) and the state of photorefractoriness. Gonadal steroid levels fluctuate during the breeding season; increasing after gonadal recrudescence and declining sharply once gonadal regression begins.
View Article and Find Full Text PDFThe premammillary nucleus (PMM) of the turkey mediobasal hypothalamus, where dopamine-melatonin (DA-Mel) neurons are localized, is a site for photoreception and photoperiodic time measurement, which is essential for the initiation of avian reproductive seasonality. In addition, this area could also be responsible for the onset and maintenance of photorefractoriness at the end of the breeding season due to the enhanced inhibitory effect of γ-aminobutyric acid (GABA). GABA is an inhibitory neurotransmitter in the central nervous system which interferes with the photosexual response in the turkey, a seasonally breeding bird.
View Article and Find Full Text PDFBackground/aims: Photoperiod is a major environmental cue in temperate-zone birds which synchronizes breeding with the time of year that offers the optimal environment for offspring survival. Despite continued long photoperiods, these birds eventually become refractory to the stimulating photoperiod and their reproductive systems regress. In this study, we characterized the role of γ-aminobutyric acid (GABA)ergic neurotransmission in modulating the response of the premammillary nucleus (PMM) to a gonad stimulatory photoperiod and the onset of photorefractoriness.
View Article and Find Full Text PDFProgesterone and progesterone receptors (PRs) are essential for the development and cyclical regulation of hormone-responsive tissues including the breast and reproductive tract. Altered functions of PR isoforms contribute to the pathogenesis of tumors that arise in these tissues. In the breast, progesterone acts in concert with estrogen to promote proliferative and pro-survival gene programs.
View Article and Find Full Text PDFThe pathway for light transmission regulating the reproductive neuroendocrine system in temperate zone birds remains elusive. Based on the evidence provided from our studies with female turkeys, it is suggested that the circadian clock regulating reproductive seasonality is located in putatively photosensitive dopamine-melatonin (DA-MEL) neurons residing in the premammillary nucleus (PMM) of the caudal hypothalamus. Melanopsin is expressed by these neurons; a known photopigment which mediates light information pertaining to the entrainment of the clock.
View Article and Find Full Text PDFBackground: The bone-tumor microenvironment encompasses unique interactions between the normal cells of the bone and marrow cavity and the malignant cells from a primary or metastasized cancer. A multitude of paracrine factors within this microenvironment such as the growth factor, TGF-beta, and the chemokine, MCP-1, are secreted by many of these cell types. These factors can act in concert to modulate normal and malignant cell proliferation, malignant cell migration and invasion and, often, mediate bone cancer pain.
View Article and Find Full Text PDFMitogen activated protein kinase phosphatase-3 (MKP-3) is a putative tumor suppressor. When transiently overexpressed, MKP-3 dephosphorylates and inactivates extracellular signal regulated kinase (ERK) 1/2. Little is known about the roles of endogenous MKP-3, however.
View Article and Find Full Text PDFJ Cell Biochem
October 2005
The protein tyrosine kinases (PTK) and the protein tyrosine phosphatases (PTPs) are enzymes which play an integral role in tyrosine phosphorylation-dependent signaling cascades. By catalyzing the phosphorylation and dephosphorylation of cellular proteins, these enzymes direct the steady-state levels of specific phosphoproteins and ultimately dictate the functional state of all cells. The importance of this type of signaling in the skeleton is accepted but poorly understood.
View Article and Find Full Text PDFOsteotesticular protein tyrosine phosphatase (OST-PTP; OST), is a signaling molecule which catalyzes the removal of phosphates from tyrosine residues. It is known to be highly regulated in bone cells and has been shown to be important for the in vitro progression from a preosteoblast to a mature, mineralizing cell. However, the in vivo expression of this phosphatase during skeletogenesis has not been examined.
View Article and Find Full Text PDFWe have capitalized on the unique properties of the skin tumor promoter palytoxin, which does not activate protein kinase C, to investigate alternative mechanisms by which major signaling molecules can be modulated during carcinogenesis. We report here that palytoxin activates extracellular signal-regulated kinase (ERK) through a novel mechanism that involves inactivation of an ERK phosphatase in keratinocytes derived from initiated mouse skin (308 cells). Use of U0126 revealed that palytoxin requires the ERK kinase MEK to stimulate ERK activity, although palytoxin did not activate MEK.
View Article and Find Full Text PDFIn mouse epidermis in vivo, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) increases gene expression of matrix metalloproteinase-13 (MMP-13), an enzyme implicated in carcinogenesis. Here we used a keratinocyte cell line (308) derived from initiated mouse skin to investigate TPA-induced MMP-13 gene expression. Use of a pharmacological inhibitor (U0126) demonstrated that extracellular signal regulated kinase (ERK) plays a major role in TPA-induced MMP-13 gene expression.
View Article and Find Full Text PDFProtein tyrosine phosphatases (PTPs) are critical regulators of cellular phosphorylation functioning in processes such as cell growth, differentiation, and adhesion. Osteotesticular PTP (OST) is the only characterized member of this superfamily whose expression is regulated in osteoblasts and critical for their in vitro differentiation. Such evidence would suggest that this molecule is a key modulator of signaling events during osteogenesis, yet little is known about its genetic regulation.
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