Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q7LGC8 (HSD)
 3,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major role of the corpus luteum is biosynthesis of progesterone. Luteal function has been investigated by following plasma progesterone concentrations and by studying ultrastructural and histochemical changes in corpora lutea. Recently, changes in enzyme activities concerned with formation and degradation of progesterone are taken into investigation in order to understand the regulation of luteal function. In rat ovaries, progestational potency of ovarian secretions has been regulated by the activity of 20 alpha-hydroxysteroid dehydrgoenase (20 alpha-HSD), Which catabolizes progesterone to 20 alpha-hydroxypregn-4-en-3-one, progestatinally inert steroid. In regressing corpora lutea, extensive conversion of progesterone to 20 alpha-hydroxypregn-4-en-3-one occurred with a marked increase in 20 alpha-HSD activity as well as a decrease in plasma progesterone concentrations. On the other hand, histochemical studies of glucose-6-phosphate dehydrogenase (G 6 PDH) and delta5-3beta-hydroxysteroid dehydrogenase (3 beta-HSD) have been investigated without any remarkable changes in corporalutea at their early stages of luteolysis. In the present study the activities of steroidogenic enzymes in corpora lutea of pregnant rats are measured after treatment with a variety of abortifacient drugs, and compared with those in corpora lutea of 1 day post partum rats which showed changes characteristic of spontaneous luteolysis. On days 7 to 9 of pregnancy, Wistar-strain pregnant rats were injected with either prostaglandin F2alpha (PGF2alpha), aminoglutethimide or clomiphene citrate (clomid). Animals were sacrificed 15 to 63 hrs. after the last injection, and implantation sites were inspected. Ovaries were removed, and corpora lutea dissected free, weighed and homogenized. The homogenate was centrifuged at 105,000g for 60 min. The supernatant solution was assayed for the activities of G 6 PDH, 6-phosphogluconate dehydrogenase (6 PGDH), malic enzyme, ATP citrate lysase, 20 alpha-HSD and pyruvate kinase. The pellet fraction was re-homogenized, and centrifugated 2,000 g for 5 min. The supernatant solution was used for the assay of 3 beta-HSD. Complete fetal resorption was observed in all rats treated with PGF2alpha, while 7 out of 15 rats (47%) treated with both PGF2alpha and LH-RH maintained pregnancy. In intact rats after treatment with both drugs, lutein cells showed ultrastructures characteristic for luteolysis, although the degree of luteolysis was greatly diminished compared with PGF2alpha-treated ones. In agreement with these ultrastructural findings, 20alpha-HSD activity in corpora lutea was maintained at a rather low level in intact rats, while it was increased moderately in aborted ones after treatment with both drugs. In PGF2alpha-treated rats, G 6 PDH activity increased to 140% and malic enzyme activity decreased to 27% of the activity in control rats. In aminoglutethimide-treated rats, the activites of G 6 PDH and malic enzyme were decreased, while 2-alpha-HSD activity was maintained at a low level...
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PMID:[Studies on the activities of steroidogenic enzymes in corpora lutea of early pregnant rats treated with abortifacient drugs (author's transl)]. 124 45

In summary, these studies have suggested that prostaglandin dehydrogenase may have a central role to play in the mechanisms which determine biologically active prostaglandin concentrations within human fetal membranes and placenta at the time of labor, at term or preterm. Moreover, our studies indicate that the regulation of PGDH may by multifactorial (figure 3). In certain regions of the membranes, we suggest that PGDH expression may be influenced by levels of anti-inflammatory and pro-inflammatory cytokines. In other regions of the membranes, we suggest that PGDH may be regulated at a transcriptional level by competing activities of progesterone and cortisol. The action of progesterone could be effected through systemically-derived steroid, or by locally synthesized steroid, acting in a paracrine and/or autocrine fashion. The effects of cortisol in placenta must be due to glucocorticoid derived from the maternal or fetal compartment, since the placenta lacks the hydroxylases required for endogenous cortisol production. However, metabolism of cortisol by 11 beta-HSD-2 reduces the potency of this glucocorticoid in placental tissue. In chorion however, cortisol may be formed locally, from cortisone, in addition to its being derived from the maternal circulation and/or from the amniotic fluid. Our current studies do not allow us to delineate whether the effects of progesterone and cortisol on PGDH are exerted through the glucocorticoid receptor (GR) or progesterone receptor (PR) or both. It is possible that through pregnancy, PGDH activity is maintained by progesterone acting either through low levels of PR in membranes, or, more likely, acting through GR. At term, elevated levels of cortisol compete with and displace progesterone from GR, resulting in inhibition of PGDH transcription and activity. In this way, local withdrawal of progesterone action would be effected within human intrauterine tissues, without requiring changes in systemic, circulating progesterone concentrations. Since glucocorticoids appear also to increase expression of prostaglandin synthesizing enzymes within the amnion and chorion, directly by upregulating PGHS-2, or indirectly through the intermediary action of a paracrine effector such as CRH, their role in coordinating processes of parturition remains central. Further understanding of the regulation of PGDH may be of therapeutic importance. For example, it is possible that PGDH activity in lower segment chorion may be reduced in those patients with premature cervical softening, or may be particularly high in those patients with an unfavorable cervix, presenting with a low Bishop score and poor progression at the time of labor. If the enzyme in this region crucially determines the passage and availability of biologically active prostaglandins from amnion and chorion to underlying cervix, then pharmacologic manipulation of PGDH activity may effectively regulate PG transfer in these clinical conditions. Glucocorticoids appear to have a central role in promoting production of agents that are uterotonic to myometrial activity. It is likely that these activities explain the transient increments in uterine contractility reported in patients receiving prenatal corticosteroids to promote fetal pulmonary maturity [11]. Recognition of this physiology suggests that careful monitoring of these patients is advised, and would argue further against repeated, indiscriminate, use of glucocorticoids in patients with an inappropriate diagnosis of threatened preterm labor.
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PMID:Prostaglandin dehydrogenase and the initiation of labor. 1034 31

A general characteristic of fetal endocrine maturation across different species is the enhanced activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis during late gestation. Precocious activation of this axis may occur when the fetus is exposed to an adverse intra-uterine environment, such as hypoxemia. HPA development is associated with increased levels of ACTH(1-39) and adrenal corticosteroids (cortisol in sheep and human) in the fetal circulation, and increased expression of mRNA encoding corticotrophin releasing hormone (CRH) in the hypothalamus, proopiomelanocortin (POMC) in the pituitary, and key steroidogenic enzymes in the fetal adrenal. At term, increased levels of cortisol act on the placenta/trophoblast derived cells to increase expression of prostaglandin synthase Type II (PGHS-II). In human gestation, cortisol also decreases expression of 15-hydroxyprostaglandin dehydrogenase (PGDH) in chorionic trophoblast cells. Increased synthesis and decreased metabolism of prostaglandin (PG) results, during late gestation, in enhanced output of primary PG, which in turn increases the activity of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) in the human fetal membranes. Increased chorionic 11 beta HSD-1 results in increased local generation of cortisol from cortisone, with further paracrine/autocrine stimulation of PG output. Increased fetal cortisol contributes to the maturation of organ systems required for postnatal extra-uterine survival. However, excessive levels of feto-placental glucocorticoid, derived from maternal administration of synthetic corticosteroids or sustained endogenous fetal cortisol production, results in intrauterine growth restriction. Fetal sheep, exposed to maternal betamethasone in late gestation, develop insulin resistance and exaggerated adrenal responses to HPA stimulation by 6-12 months postnatal life. Thus, the level of fetal HPA activity is crucial not only for determining gestation length, but may also predict pathophysiologic adjustments in later life.
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PMID:The fetal placental hypothalamic-pituitary-adrenal (HPA) axis, parturition and post natal health. 1173 3

Increased uterine contractility at term and preterm results first from activation and then stimulation of the myometrium. Activation can be provoked by mechanical stretch of the uterus, and by an endocrine pathway resulting from increased activity of the fetal hypothalamic-pituitary-adrenal axis. In sheep fetuses, increased cortisol output during pregnancy regulates expression of prostaglandin synthase type 2 (PGHS-2) in the placenta in an oestrogen-independent manner, resulting in increased concentrations of prostaglandin E2 (PGE2) in the fetal circulation. Later increases in maternal uterine expression of PGHS-2 require increases in oestrogen and lead to increased concentrations of PGF(2alpha) in the maternal circulation. Thus, regulation of PGHS-2 at term is differentially controlled in fetal (trophoblast) and maternal (uterine epithelium) tissue. This difference may reflect expression of glucocorticoid receptor but not oestrogen receptor (ER) in placental trophoblast cells. In women, cortisol also contributes to increased prostaglandin production in fetal tissues through upregulation of PGHS-2 (amnion and chorion) and downregulation of 15-OH prostaglandin dehydrogenase (PGDH; chorion trophoblasts). The effect of cortisol on expression of PGDH in the chorion reverses a tonic stimulatory effect of progesterone, potentially through a paracrine or autocrine action. In membranes, cortisol may be derived from cortisone through activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1, in addition to secretion from the maternal or fetal adrenal glands. In placenta, 11beta-HSD-2 oxidase activity predominates and expression of this enzyme is reduced with hypoxaemia and in placentae from pre-eclamptic pregnancies. In these circumstances, increased concentrations of maternal cortisol may cross into the fetal compartment, contributing to growth restriction and programming later life disease.
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PMID:Prostaglandins and mechanisms of preterm birth. 1209 Sep 13