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It is increasingly apparent that GnRH-II acts as an autocrine/paracrine regulator in non-pituitary tissues, in addition to its role in the regulation of gonadotropin synthesis, and is an important player in cancer cell biology. High levels of GnRH-II and GnRHR in malignant ovarian tumors as compare…
Ovarian cancer is the sixth most common cancer and the fifth leading cause of cancer-related death among women in developed countries. There is increasing evidence suggesting that the hormonal environment of the normal ovarian surface epithelium (OSE) and ovarian epithelial cancer (OEC) cells is as…
There is increasing evidence to suggest that activin can function as an autocrine/paracrine regulator in various tissues, including the reproductive system. At the cellular level, activin acts via a family of activin receptor (ActR) subtypes which includes two type I (ActRI and ActRLB) and two type…
The studies undertaken herewithin sought to characterize the pattern of regulation of the gonadotrophin-releasing hormone receptor (GnRH-R) mRNA levels in the rat ovary. The demonstration of gonadotrophin-releasing hormone (GnRH) transcripts in steroidproducing and steroid-dependent tissues suggest…
This thesis investigated the expression and regulation of cytochrome P450s, aromatase (P450arom) and cholesterol side chain cleavage (P450scc) enzyme mRNAs in human granulosa-luteal cells using reverse transcription-polymerase chain reaction (RT-PCR). The two enzymes are instrumental in steroid hor…
The present study was conducted to investigate the hypothesis that membrane phosphoinositide breakdown may participate in the actions of luteinizing hormone-releasing hormone (LHRH) on hormone production in the rat ovary. In granulosa cells prelabeled with [³H]-arachidonic acid or [³H]-inositol, tr…
Activin A (homodimer of inhibin βA-subunit) is known to increase inhibin βB-subunit and inhibin B (heterodimer of inhibin α- and βB-subunit) levels and decrease progesterone accumulation in human granulosa cells. Growth differentiation factor 9 (GDF9) is a potent paracrine regul…
An excitatory role for norepinephrine (NE) in the regulation of luteinizing hormone (LH) release was first suggested when it was demonstrated that noradrenergic receptor antagonists were able to block ovulation. More recently it has been proposed that NE has both an excitatory role and an inhibitor…
It is well established that LH action is mediated primarily by adenylate cyclase/cAMP. Conversely, the role of inositol phosphate/calcium in LH signalling has only recently been investigated. We examined the effects of gonadotrophins on intracellular calcium mobilisation in HEK293 cells transiently…
The gonadotropin - releasing hormone (GnRH) receptor is a plasma membrane associated receptor and a member of the GTP - binding protein coupled receptor family. The interaction of the ligand, GnRH, and the GnRH receptor is a critical event in the endocrine control of reproduction. This coupling sti…
Remodeling of the endometrial extracellular matrix, which occurs during the early stages of pregnancy in the human, is mediated by the temporal expression of urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMP) in both the maternal and fetal compartments and counterbalance…
In the present study, the effects of clomiphene citrate (CC) on ovulation, ovarian growth and ovarian steroidogenesis were examined. Ovulation in rats in response to PMSG was completely blocked by administration of three daily treatments of 1.0 mg CC/rat, but was restored by administration of hCG a…
Loss of BRCA1/BRCA2 function through genetic or epigenetic mechanisms is common in epithelial ovarian carcinomas (EOC), but because there are multiple potential mechanisms of loss, the overall frequency is unknown. We characterized loss of BRCA1/BRCA2 at the DNA, RNA and protein level from an unsel…
This study examined primary defects and related mechanisms leading to impaired fertility following superovulation with exogenous gonadotropin. Experiments were designed to address the ovulatory response, oocyte quality (gross morphology and nuclear maturation) and embryo development with reference …
Homeobox genes, which code for families of transcription factors, act at the top of genetic hierarchies. HOX genes specify positional identity during development, and in adult tissues, regulate differentiation and proliferation. Most ovarian carcinomas are derived from the ovarian surface epitheliu…
n approximately 40% of ovarian cancers, PIK3CA, which encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K) is amplified. This amplification correlates with increased PIK3CA transcription, p110α protein expression, and PI3K activity. Moreover, PIK3CA is implicated as…
Ovarian cancer is the most lethal gynecological cancer in the Western world, but comparatively little is known about its development. Epithelial ovarian carcinomas are thought to originate in the ovarian surface epithelium (OSE), i.e. the mesothelium covering the ovary, but experimental evidence fo…
The common epithelial ovarian tumors appear to arise from the ovarian surface epithelium (OSE), which is a simple squamous-to-cuboidal meso^helium covering the ovary. The exact mechanism of ovarian tumorigenesis is not well known even though this disease is the most frequent cause of cancer death i…
Superovulation causes detrimental effects, including embryonic loss and implantation failure. This study determined potential roles for insulin-like growth factor (IGF-I) in uterine environment regulation and preimplantation development, in conjunction with the detrimental effects of superovulation…
Nuclear receptors including estrogen receptors (ERs) and progesterone receptors (PRs) are activated by their ligands as well as by signaling pathways in response to peptide hormones and growth factors. In gonadotrophs, gonadotropin releasing hormones (GnRHs) act via the GnRH receptor (GnRHR). Both …