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The Study of Steroid Regulations of Placental CRH Gene Transcription and Their Mechanisms

Author: Hou
Tutor: NiZuo
School: Second Military Medical University
Course: Physiology
Keywords: Corticotropin- releasing hormone Estrogen Progesterone Placenta Gene transcription
CLC: R33
Type: Master's thesis
Year: 2003
Downloads: 56
Quote: 1
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Abstract

Placental hormone secretion plays an important role in human pregnancy. Studies have shown that human placenta synthesis and secretion of a hypothalamic neuroendocrine hormone - corticotropin-releasing the hormone (corticotropinreleasing hormone, CRH), this hormone will not only affect the development and maturation of the fetus, but also through a variety of ways to participate in childbirth start, and preterm delivery, fetal intrauterine growth retardation and other diseases. Therefore, the study of the mechanism of the synthesis and secretion of placental CRH, not only helps to reveal the the human childbirth startup mechanism and the mechanism of fetal growth and development, but also for preterm birth, intrauterine growth retardation provide a theoretical basis for treatment of diseases such. The body of a variety of factors may regulate placental CRH secretion of. Closely related to the pregnancy process estrogen and progesterone on the CRH gene transcription regulation of placental cells and its mechanism is not yet clear. In this study, the use of primary cultured human placental trophoblast cells to carry out a study of the following three aspects: 1 observe estradiol (estradiol, E ₂) inhibition of placental CRH gene expression occurred at the transcriptional level; clear which estrogen receptor subtype mediates the effect of estrogen; determine the CRH gene and estrogen regulation related to the role of the DNA sequence. 2 primary placental cells, first observed in the glucocorticoid receptor (GR) and progesterone receptor (PR) expression, on this basis, a further study of progesterone (progesterone, P ₄ GR and PR progesterone in regulating the activity of placental CRH gene transcription) regulation of placental CRH gene transcription;, and CRH gene promoter regulation relating to the role of progesterone response element. 3, the observation of PKA regulatory role of PKC agonists on placental CRH gene transcription as well as estrogen and progesterone PKA, PKC-induced CRH gene transcription. The main results and conclusions are as follows: 1. Estrogen regulation of placental CRH gene transcription activity: E ₂ (10 ^{-7 M) can inhibit the transcription of the CRH gene, this role has a time-and dose-dependent manner . Estrogen receptor antagonist ICI182780 (10 ^{-6 M) will not only be able to block the E ₂ inhibition of placental CRH gene transcription activity, and also promote CRH gene transcription. The ERα, ERβ expression vector with CRH reporter gene, transfected placental cells, E ₂ and ICI only on ERα overexpression of CRH gene transcription activity of the cells have a significant role in regulating Description estrogen receptor antagonist role of placental CRH gene transcription mediated by ERα. Determined using the 5 'end of the missing estrogen adjust the role of the DNA fragment, the results show that the nucleotide sequence located CRH promoter region between -248 to -213 is the Journal Chinese Summary estrogen inhibiting CRH gene transcription key sequence. This the sequence shared CAMP response element (CAMPresponse ele Can nt, CRE) mutations, the role of estrogen disappeared. The estrogen can also inhibit containing CRE rabbit globin gene transcription and estrogen inhibit CRH gene transcription through the CRE in the promoter of the gene. 2. Progesterone regulation of placental CRH gene transcription activity: Western Blot method shows the placental cells express a large number of plus and a small amount of knock A and mB to knock B expression greater than called A expression. Held by progesterone receptor antagonist RU38486 (10 - 'M) in processing or trilostane (10 -' M) to inhibit the generation of endogenous progesterone can promote CRH gene transcription, and inhibit RU or the trilostane of placental CRH gene role in promoting transcription, suggesting that endogenous progesterone inhibit placental CRH gene transcription. PRA, PRB, and GR expression vector with CRH reporter gene, transfected into placental cells, when PRA or GR overexpression, P. *-V) can inhibit CRH gene transcription, can also block the RU and trilostane Upregulation of CRH gene transcription; cells overexpressing PRB, RU38486 (10 - 'M) and trilostane (10 -' M) but inhibited CRH gene transcription P/10-) but raised the CRH gene transcription activity. progesterone placental CRH gene transcription regulation is the result of joint action with the PRA, PRB, and GR progesterone on placental gene transcription inhibitory effect is achieved through the CRH gene promoter CRE shows of CRH gene CRE groups hormonal regulation of placental CRH gene critical components. 3.PKA activator 8 - B, CAMP (10 - ' M and outer C activator PMA (10 - 'M) can promote placental the mH gene transcription the CRE than A, PKC promote the key components of the H gene expression, indicating that placental cells than A and PKC signaling pathways in CRE cross dialogue with the public and P / system PKA and PKC upregulation of CRH gene. above results show that: 1) estrogen inhibition of the the placental H gene transcription of CRH gene CRE estrogen inhibition of CRH gene expression of key components, this effect is mediated by the ER a 2) and progesterone also inhibit CRH gene transcription, progesterone, GR, PRA inhibit CRH gene expression, with PRB role to promote CRH gene expression, the role of progesterone on the CRH gene achieved through the CRE in the promoter of the gene. 3) PKA and PKC through the induced the mH gene expression than the H gene mE components, suggesting the A and Team C signaling pathway in the cross-CRE at dialogue.}}

The Study of Steroid Regulations of Placental CRH Gene Transcription and Their Mechanisms

Abstract

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