Disease relevance of Pregnenedione

• The reproductive hormone defects of Lats1-/- mice are reminiscent of isolated LH-hypogonadotropic hypogonadism and corpus luteum insufficiency in humans [1].
• In adulthood, angiogenesis takes place during corpus luteum formation and in pathological conditions such as wound healing, diabetic retinopathy, and tumor-igenesis [2].
• Corpus luteum hemorrhage. Cause of acute abdominal pain in patients receiving anticoagulant therapy [3].
• Detailed studies of urinary steroids in patients with breast cancer and normal controls have shown that abnormal aging processes and depressed corpus luteum function were associated with the presence of this form of cancer [4].
• In nine women with unruptured ectopic pregnancy, prostaglandin F2 alpha was injected under laparoscopic control into the affected oviduct and in eight patients also into the ovary containing the corpus luteum [5].
• Over the last decade, there have been a growing number of studies showing that exogenous administration of progesterone or some of its metabolites can be successfully used to treat traumatic brain and spinal cord injury, as well as ischemic stroke [6].
• We find spontaneous preterm labor in the absence of progesterone withdrawal in 15-hydroxyprostaglandin dehydrogenase hypomorphic mice [7].

Psychiatry related information on Pregnenedione

• Female llamas ovulate in response to copulation, and progesterone secretion by the corpus luteum indicates recent ovulation (mating) and, or, pregnancy [8].
• Effects of prolonged luteinizing hormone-releasing hormone therapy on follicular maturation, ovulation and corpus luteum function in amenorrhoeic women with anorexia nervosa [9].

High impact information on Pregnenedione

• However, OT is also synthesized in peripheral tissues, e.g., uterus, placenta, amnion, corpus luteum, testis, and heart [10].
• If pregnancy does not occur, the corpus luteum must regress to allow follicular growth and ovulation and the reproductive cycle begins again [11].
• Hysterectomy in these nonprimate species causes maintenance of the corpora lutea, whereas in primates, removal of the uterus does not influence the cyclical regression of the corpus luteum [12].
• In primates, oxytocin and its receptor and PGF2alpha and its receptor have been identified in the corpus luteum and/or ovary [12].
• After ovulation, oocytes resume meiosis and granulosa cells retained in the follicle differentiate into steroidogenic cells, forming the corpus luteum [13].

Chemical compound and disease context of Pregnenedione

• Anti-MIF antibody prevented P-mediated up-regulation of TNF-alpha, improved TNBS colitis, and enhanced plasma corticosterone [14].
• Effects of EB and P on myeloperoxidase activity and MIF concentration were also assessed at 7 days in dextran sulfate sodium-induced colitis [14].
• Susceptibility to drug-induced coronary vasospasm in rhesus monkeys increases after removal of the ovaries and can be normalized by adding back physiological levels of estradiol-17ss (E2) and/or natural progesterone (P) in vivo as reported recently by our group [15].
• We hypothesize that vascular hyperreactivity, which may be a critical factor involved in the increased incidence of coronary artery vasospasm and ischemic heart disease in postmenopausal women, can be normalized by E2 and/or P through direct actions on coronary artery vascular muscle cells [15].
• The concordance rate in simultaneous ER assays was 85%; however, we found a considerable high discordance rate for PgR in primary tumor and lymph node metastasis (25%) [16].

Biological context of Pregnenedione

• In the ovary, tissue remodeling is requisite for growth and expansion of the follicle, breakdown of the follicular wall during the ovulatory process, transformation of the postovulatory follicle into the corpus luteum, as well as the structural dissolution of the corpus luteum during luteal regression [17].
• They may serve as a redundant system to assure that there is sufficient secretion of the primary corpus luteum to maintain pregnancy until the placenta assumes its role as the principal steroidogenic organ of gestation [18].
• Progesterone (PRE) or glucocorticoid receptor (GRE) DNA binding sites are often found clustered with binding sites for other transcription factors [19].
• The clinical implications of these primate studies may be far-reaching because they indicate new potential for childbearing by otherwise infertile or sterile women who have a competent uterus but lack the hormonal milieu provided by ovarian follicular maturation and corpus luteum function in the normal menstrual cycle [20].
• Prolactin interferes with the function of the corpus luteum, as was demonstrated by repeatedly finding a short luteal phase in the ovulatory cycles of two hyperprolactinaemic women after prolactin supression by bromocriptine had been discontinued [21].

Anatomical context of Pregnenedione

• The marked inhibitory effects of GnRH and its agonists on corpus luteum function suggest that these compounds could exert direct actions by binding to specific receptors on luteal cells [22].
• The conceptus within the uterus, therefore, is believed to produce a substance or substances which directly or indirectly prolong the lifespan of the corpus luteum and prevent a return to ovarian cyclicity [23].
• Implication of absence of HCG-like gonadotrophin in the blastocyst for control of corpus luteum function in pregnant rabbit [24].
• The development of new blood vessels (angiogenesis) is required for many physiological processes including embryogenesis, wound healing and corpus luteum formation [25].
• The alterations in morphology and function of the ovarian follicle as it matures, ovulates, and becomes a corpus luteum are dramatic [26].

Associations of Pregnenedione with other chemical compounds

• GnRH-induced interruption of reproductive cycles and pregnancy is associated with diminished progesterone production, implying defective function of the corpus luteum [22].
• These tissues include ovarian steroidogenic theca cells and lutein cells of the corpus luteum, testosterone-producing Leydig cells of the testis, steroidogenic cells confined to the zona reticularis of the adrenal cortex, and progesterone-producing cells of the placenta [27].
• From this and previous data, we conclude that the increases of estradiol secretion associated with the follicular maturation and corpus luteum formation represent a major component of the feedback signal in the modulation of cyclic gonadotropin release occasioned in a large measure by the augmented pituitary sensitivity to LRF [28].
• Stepwise regression analysis indicated that variations in the levels of progestin binding accounted for 17% (P less than 0.01) and variations in the levels of triamcinolone binding for 3% (P = 0.05) of the variation observed in PAA [29].
• Administration of E or P to ovariectomized females induced C/EBPbeta expression in both uterine epithelium and stroma, showing a dual regulation of this gene by these hormones [30].
• We found no evidence that human or fish mPRs regulate cAMP production or MAPK (ERK1/2 or p38) activation upon progesterone stimulation [31].
• In RMG, membrane-impermeable progesterone conjugate induced calcium influx and subsequent phosphatidylinositol 3-kinase-mediated phosphorylation of PKC and ERK-1/2 [32].
• The work illustrates the relevancy of the mouse model for understanding endometrial vascular remodeling during the menstrual cycle and in response to the clinically important progesterone receptor antagonist RU486 [33].
• In mammals, the Purkinje cell actively synthesizes progesterone de novo from cholesterol during neonatal life when cerebellar neuronal circuit formation occurs [34].

Gene context of Pregnenedione

• CDK4(-/-) mice survived embryogenesis and showed growth retardation and reproductive dysfunction associated with hypoplastic seminiferous tubules in the testis and perturbed corpus luteum formation in the ovary [35].
• VPF/VEGF likely also contributes to the angiogenesis and connective tissue stroma generation that accompany corpus luteum/corpus albicans formation [36].
• RNA blot and in situ hybridization analyses demonstrated that the PGF receptor transcripts are abundantly expressed in luteal cells of corpus luteum and in a lesser amount in kidney, heart, stomach, and lung [37].
• The current study investigates the activation in vivo and regulation of the expression of components of the p38 mitogen-activated protein kinase (MAPK) pathway during gonadotropin-induced formation and development of the rat corpus luteum, employing a sequential PMSG/human CG (hCG) treatment paradigm [38].
• However, we observed that LIF can only partially resume implantation in P4-primed, delayed implanting mice in the absence of estrogen, suggesting LIF induction is one of many functions that are executed by estrogen for implantation [39].
• Progesterone inhibits the induction of TNF synthesis by viral infection and virus or gp-120-induced TNF transcription [40].
• Mining this informational resource for rapidly induced genes, we identified "inhibitor of differentiation 4" (Id4) as a new molecular target acutely induced by progesterone exposure [41].
• Using siRNA-mediated knockdown of both DKK1 and FOXO1, progesterone inhibition of Wnt signaling was partly circumvented [42].

Analytical, diagnostic and therapeutic context of Pregnenedione

• Bleeding from corpus luteum should be considered in differential diagnosis of low abdominal pain in women of reproductive age receiving anticoagulant therapy [3].
• The antibodies were competent for neutralizing the biological activity of HCG in the mouse uterine weight gain assay, the ventral prostate weight gain assay, and the radioligand assay for binding of 125I-labeled HCG to receptors on corpus luteum [43].
• Using the polymerase chain reaction, mRNA encoding the FP(B) isoform was identified in the ovine corpus luteum [44].
• In female animals, the effect of ovariectomy was less striking than in the male, a 25% increase (P less than 0.001) being observed [45].
• In this study, we investigated whether the ovarian steroids, estrogen (E) and progesterone (P) regulate SERT binding, intracellular distribution, and function using [(3)H]citalopram ligand binding with quantitative autoradiography, immunofluorescence histochemistry with confocal microscopy and [(3)H]serotonin uptake, respectively [46].

References