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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our understanding of Polycystic Ovary Syndrome (PCOS) has been hampered by varying diagnostic criteria, and ignorance of the etiology of the syndrome. PCOS women are uniquely insulin resistant and obesity aggravates this underlying predisposition to insulin resistance. Diagnostic criteria which focus on hyperandrogenism and/or menstrual irregularity are more likely to identify insulin resistant women, than such criteria as abnormal gonadotropin secretion or ovarian morphology. The lack of a clear etiologic mechanism to the syndrome has led to a multitude of symptom-oriented treatments with few therapies improving all aspects of the endocrine syndrome of PCOS. Improving insulin sensitivity has become established as a baseline treatment strategy in PCOS. There are, however, few randomized controlled trials of adequate power to provide an evidence based guide to treatment in PCOS.
Mol Cell Endocrinol 2001 Nov 26
PMID:Polycystic ovary syndrome: the new millenium. 1169 44

Leptin, the 'obese' protein, is found in cultured granulosa cells derived from human pre-ovulatory follicles. However, the occurrence of leptin has not been studied in intact ovaries, either normal or polycystic, until now. Paraffin sections from 25 human ovaries of different cycle stages and 25 wedge resections of polycystic ovaries were investigated by means of immunochemistry. Additionally, three ovaries were available for reverse transcription-polymerase chain reaction analysis. Leptin-positive cells were located in the granulosa cells of pre-antral follicles, and distinctly in the thecal layer of intact and regressing antral follicles. In the corpus luteum (CL) in the developmental stage, the former epithelioid leptin-positive thecal cells became fibroblast-like in the septum. In the CL of the secretory stage, single leptin-positive cells were detected between luteal cells. In polycystic ovaries, leptin-positive cells were noted both in the hypertrophied thecal layer and in the luteinized granulosa layer. Our findings on leptin expression at the protein level were confirmed by a positive mRNA signal for leptin in granulosa cells and in the CL. Additionally, mRNA of the full-length leptin receptor OB-R and of the short isoforms B219.1-B219.3 was identified in granulosa cells and the CL, as well as in the cortex and medulla. We conclude that leptin is produced in the ovary and may act in autocrine and paracrine ways.
Mol Hum Reprod 2001 Dec
PMID:Evidence of leptin expression in normal and polycystic human ovaries. 1171 91

Polycystic ovary syndrome (PCOS) is characterized by increased ovarian androgen production. We have developed a strategy to identify differentially transcribed genes in PCOS theca cells. Using long-term cultures of normal and PCOS theca cells, we are characterizing the complete repertoire of differentially transcribed genes, the common transcription factor mediators, and the signal transduction cascade(s) that are abnormal in PCOS theca cells. The latter will be interrogated for mutations/genetic variants linked to PCOS.
Mol Cell Endocrinol 2002 Jan 25
PMID:Strategies to elucidate the mechanism of excessive theca cell androgen production in PCOS. 1190 Aug 94

Hyperandrogenaemia in women presents in a variety of ways, including problems with the reproductive system. The commonest cause is polycystic ovary syndrome (PCOS), a condition found in 5-10% of all women. PCOS has origins that are genetic and environmental but the end organ, the ovary, exhibits excessive androgen production with enhanced sensitivity to luteinising hormone and insulin. Interventions include approaches that target both these hormones as well as the ovary itself.
Mol Cell Endocrinol 2002 May 31
PMID:Hyperandrogenaemia and the ovary. 1204 25

Analysis of a paper by Severinghaus et al. (see text) has already shown that sea level oxygen delivery (D(a)O(2)) is sustained 8 h after ascent to 3810 m, despite low arterial oxygen content (C(a)O(2)), largely as a result of increased cerebral blood flow (CBF). The present study extends the analysis to show that D(a)O(2) is also sustained after 3 and 5 days at altitude, despite a progressively falling CBF. It is shown that this later compensation is a result of the improvement in C(a)O(2), which accompanies acclimatisation. Since less than 3% rise in haemoglobin occurred, the rise in C(a)O(2) was predominantly respiratory. It has been shown elsewhere that as acclimatisation occurs, the fall in arterial PCO(2) (P(a)CO(2)) results in increased arterial PO(2) (P(a)O(2)) until they are related according to P(a)CO(2)=0.25 P(a)O(2)+/-15 mmHg. The results from Severinghaus et al. at 3 and 5 days fall close to this line. We also report arterialised capillary blood gases from 18 normal subjects, acclimatised at 5300 m. The values fall in a group centred on the same line. In summary, soon after arrival at altitude (8 h), cerebral oxygen delivery is largely sustained by an increase in CBF. The present study shows that, although CBF declines during the 3-5 day period, D(a)O(2) is sustained as a result of the improvement in C(a)O(2), which is mainly due to respiratory acclimatisation.
Comp Biochem Physiol A Mol Integr Physiol 2002 May
PMID:Cardiovascular and respiratory adjustments at altitude sustain cerebral oxygen delivery -- Severinghaus revisited. 1206 13

To determine the influence of FSH receptor variants Thr307-Asn680 (TN) and Ala307-Ser680 (AS) on ovarian function, we investigated the frequency of these gene polymorphisms by using restriction fragment length polymorphism analysis and observed their effects on clinical manifestations. In a population of 522 Japanese women, the overall frequency of TN/TN (NN), TN/AS (NS), and AS/AS (SS) was 41.0, 46.9 and 12.1% respectively. In polycystic ovary patients, the NS population was significantly larger when compared with the spontaneously ovulating group (66.7 versus 43.5%, P < 0.05). In the SS group, a significantly higher (46%) basal level of serum FSH was observed as compared with that in the NS group (P < 0.05). A higher dose of the exogenous gonadotrophin was required to achieve ovulation induction in the SS group as compared with the NS group (P < 0.05). At the time of hCG administration, estradiol levels per oocyte retrieved for IVF in the SS group were significantly lower as compared with the levels in the NS and NN groups (P < 0.05). There were no significant differences in FSH-stimulated cAMP production and PI turnover as well as ligand-binding affinity between the two receptor isoforms when overexpressed in transfected 293T cells. These results suggest that although FSH receptor polymorphisms have no discernible effect on FSH receptor function in vitro, there are associations between the genotype and some aspects of patient status.
Mol Hum Reprod 2002 Oct
PMID:Genetic and functional analyses of polymorphisms in the human FSH receptor gene. 1235 37

It is known that atrial natriuretic peptide (ANP) is released from cardiac myocyte and other stores during hypoxia and is involved in pulmonary-cardiovascular reflexes and in natriuresis and diuresis. Since the carotid body initiates hypoxic chemoreflexes, we hypothesized that ANP could potentiate the hypoxic stimulation of the carotid body chemoreceptor in vivo. We studied the effect of close intra-arterial injection of ANP on carotid chemoreceptor activity in anesthetized male cats which were paralyzed and artificially ventilated. Graded doses of ANP (0-10 nmoles) were administered by intra-arterial injections and they produced an excitatory response. Single dose of ANP (6.5 nmoles) at four steady-state levels of arterial PO(2), at constant PCO(2), produced increases of chemoreceptor activity. This increase of chemoreceptor activity with ANP in the presence of CO(2)-HCO(3)(-) in vitro could make a difference from those without CO(2)-HCO(3)(-) in vivo.
Comp Biochem Physiol A Mol Integr Physiol 2003 Jan
PMID:Atrial natriuretic peptide stimulates cat carotid body chemoreceptors in vivo. 1250 4

Androgens and estrogens are made from dehydroepiandrosterone (DHEA), which is made from cholesterol via four steps. First, cholesterol enters the mitochondria with the assistance of the steroidogenic acute regulatory protein (StAR). Mutations in the StAR gene cause congenital lipoid adrenal hyperplasia. Second, within the mitochondria, cholesterol is converted to pregnenolone by the cholesterol side chain cleavage enzyme, P450scc. Third, pregnenolone undergoes 17alpha-hydroxylation by microsomal P450c17. Finally, 17-OH pregnenolone is converted to DHEA by the 17,20 lyase activity of P450c17. The ratio of the 17,20 lyase to 17alpha-hydroxylase activity of P450c17 determines the ratio of C21 to C19 steroids produced. This ratio is regulated post-translationally by at least three factors: the abundance of the electron-donating protein P450 oxidoreductase, the presence of cytochrome b(5), and the serine phosphorylation of P450c17. Study of these and related factors may yield important information about the pathophysiology of adrenarche and the polycystic ovary syndrome (PCOS).
Mol Cell Endocrinol 2002 Dec 30
PMID:Androgen biosynthesis from cholesterol to DHEA. 1257 9

The importance of blood hemoglobin to aquatic oxygen uptake by turtles (Chrysemys picta bellii) submerged in aerated water at 3 degrees C was tested by comparing the responses of anemic turtles (hematocrit approximately 6%) to turtles with normal hematocrits (hematocrit approximately 33%). All turtles were submerged for 42 days and blood samples were collected at 0, 7, 21, 32 and 42 days. Blood was analyzed for pH, PCO(2), PO(2), hematocrit, hemoglobin concentration ([Hb]) and plasma was analyzed for concentrations of lactate, glucose, Na(+), K(+), Ca(2+) and Mg(2+). Plasma [HCO(3)(-)] was calculated. [Hb] correlated closely with hematocrit levels. [Lactate] reached higher final values in anemic turtles (34.5+/-5.3 mmol l(-1)) than in normal turtles (14.5+/-4.6 mmol l(-1)) indicating a greater reliance of the anemic animals on anaerobic metabolism. Both groups compensated for acidosis by reduced PCO(2) and anemic turtles also had increased [Ca(2+)] and [Mg(2+)]. Blood pH fell significantly in the anemic turtles but not in the controls. Although the data indicate that the anemic turtles relied more on anaerobic metabolism than the controls, the effect was much less than expected on the basis of the reduced blood O(2) carrying capacity. Possible compensatory mechanisms utilized by the anemic turtles to minimize anaerobic metabolism are discussed.
Comp Biochem Physiol A Mol Integr Physiol 2003 Aug
PMID:Effects of experimental anemia on blood ion and acid-base status of turtles during submergence in aerated water at 3 degrees C. 1289 May 49

Compensatory hyperinsulinemia stemming from peripheral insulin resistance is a well-recognized metabolic disturbance that is at the root cause of diseases and maladies of Syndrome X (hypertension, type 2 diabetes, dyslipidemia, coronary artery disease, obesity, abnormal glucose tolerance). Abnormalities of fibrinolysis and hyperuricemia also appear to be members of the cluster of illnesses comprising Syndrome X. Insulin is a well-established growth-promoting hormone, and recent evidence indicates that hyperinsulinemia causes a shift in a number of endocrine pathways that may favor unregulated tissue growth leading to additional illnesses. Specifically, hyperinsulinemia elevates serum concentrations of free insulin-like growth factor-1 (IGF-1) and androgens, while simultaneously reducing insulin-like growth factor-binding protein 3 (IGFBP-3) and sex hormone-binding globulin (SHBG). Since IGFBP-3 is a ligand for the nuclear retinoid X receptor alpha, insulin-mediated reductions in IGFBP-3 may also influence transcription of anti-proliferative genes normally activated by the body's endogenous retinoids. These endocrine shifts alter cellular proliferation and growth in a variety of tissues, the clinical course of which may promote acne, early menarche, certain epithelial cell carcinomas, increased stature, myopia, cutaneous papillomas (skin tags), acanthosis nigricans, polycystic ovary syndrome (PCOS) and male vertex balding. Consequently, these illnesses and conditions may, in part, have hyperinsulinemia at their root cause and therefore should be classified among the diseases of Syndrome X.
Comp Biochem Physiol A Mol Integr Physiol 2003 Sep
PMID:Hyperinsulinemic diseases of civilization: more than just Syndrome X. 1452 33


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