A comparison of serum androgens in pre-eclamptic and normotensive pregnant women during the third trimester of pregnancy

Sharifzadeh, Fatemeh; Kashanian, Maryam; Fatemi, Farin

doi:10.3109/09513590.2012.683061

Cited by 36 publications

(28 citation statements)

References 15 publications

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“…[28][29][30][31][32] Adverse pregnancy outcomes, such as preeclampsia, miscarriage, gestational diabetes mellitus, and preterm birth, have been suggested to be correlated with excess androgen. 9 Literature evidence [5][6][7][8] and the present study have demonstrated the elevated T 0 and repressed E 2 circulating level in preeclamptic patients, and here, our study further showed the enhanced 17β-HSD3 and downregulated aromatase expression in PE placenta. The data strongly indicate that the productions of T 0 and E 2 in preeclamptic placentas are imbalanced.…”

Section: Discussionsupporting

confidence: 79%

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Testosterone Represses Estrogen Signaling by Upregulating miR-22

Shao

Liu

et al. 2017

Hypertension

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P reeclampsia (PE), affecting ≈5% to 7% of pregnancies worldwide, is a multisystem syndrome that occurs during the third trimester of human pregnancy, and it is a leading cause of maternal and perinatal morbidity and mortality. [1][2][3][4] Placental deficiencies are widely recognized as the principal pathological origin of the disorder.Preeclamptic patients usually present with high circulating testosterone and reduced estradiol production during gestation, and therefore, they are considered to experience endocrine disorders. [5][6][7][8] Physiologically, the circulating testosterone and estradiol levels in pregnant women increase from the first trimester and are further elevated toward the end of pregnancy. 9 The placenta is an important source of steroid hormone production throughout gestation, although the ovarian luteal cells have that role in early pregnancy. The placenta can manufacture pregnenolone and express several enzymes that are fundamentally required for the biosynthetic conversion of cholesterol to androgens and estrogens, such as CYP17 (17α-hydroxy/17,20-lyase), 3β-HSD (3β-hydroxysteroid dehydrogenase), 17β-HSD, and aromatase. Specifically, the placental aromatase acts to convert androstenedione (A 4 ) into estrone (E 1 ), and testosterone (T 0 ) into 17β-estradiol (E 2 ), and 17β-HSD3 works to convert A 4 into T 0 .9 The aberrantly increased testosterone level and decreased estradiol Abstract-Preeclampsia, a multisystem syndrome occurring during mid-to late gestation in humans, is a leading cause of maternal and perinatal morbidity and mortality. Patients usually present with high circulating testosterone and reduced estradiol production, but the mechanisms remain unclear. Revealing the mechanism that modulating the imbalance of testosterone and estradiol in preeclampsia is of great value in understanding the cause of the disease. The placenta is the predominant source of steroid hormone production during gestation, and we observed markedly increased 17β-HSD3 (17β-hydroxysteroid dehydrogenase 3) levels and downregulated aromatase expression, the key enzymes responsible for synthesis of testosterone and estradiol, respectively, in preeclamptic placentas compared with controls. Furthermore, we found a significant upregulation of microRNA (miR)-22 in preeclamptic placentas. In a trophoblast cell line, JEG-3 cells, testosterone repressed the expression of aromatase and estrogen receptor α and the production of estradiol while promoting miR-22 expression. miR-22 directly targeted and inhibited estrogen receptor α expression while indirectly decreasing aromatase expression and estradiol production by interfering with estrogen receptor α signaling. Furthermore, inhibition of miR-22 expression significantly reversed the inhibitory effect of testosterone on de novo estradiol synthesis in human trophoblastic cells. The findings reveal a mechanism underlying the balanced production of androgen and estrogen modulated by miR-22 in the human placenta and provide new insights into the pathogenesis of preeclam...

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Section: Discussionsupporting

confidence: 79%

“…[5][6][7][8] Physiologically, the circulating testosterone and estradiol levels in pregnant women increase from the first trimester and are further elevated toward the end of pregnancy. 9 The placenta is an important source of steroid hormone production throughout gestation, although the ovarian luteal cells have that role in early pregnancy.…”

mentioning

confidence: 99%

Testosterone Represses Estrogen Signaling by Upregulating miR-22

Shao

Liu

et al. 2017

Hypertension

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“…The mechanism linking the two hormonal axes is poorly understood and, interestingly, has not been considered or explored during pregnancy. Increased T levels in the maternal circulation at third trimester have been associated with the incidence of PE, suggesting T as a predictive marker (Ghorashi and Sheikhvatan, 2008; Lorzadeh and Kazemirad, 2012; Sharifzadeh et al , 2012; Simsek et al , 2012). In this context, placentae from preeclamptic pregnancies have higher expression levels of AR in both male and female fetuses (Sathishkumar et al , 2012).…”

Section: Resultsmentioning

confidence: 99%

Androgens in pregnancy: roles in parturition

Makieva

Saunders

Norman

2014

Human Reproduction Update

175

143

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BACKGROUNDUnderstanding the physiology of pregnancy enables effective management of pregnancy complications that could otherwise be life threatening for both mother and fetus. A functional uterus (i) retains the fetus in utero during pregnancy without initiating stretch-induced contractions and (ii) is able to dilate the cervix and contract the myometrium at term to deliver the fetus. The onset of labour is associated with successful cervical remodelling and contraction of myometrium, arising from concomitant activation of uterine immune and endocrine systems. A large body of evidence suggests that actions of local steroid hormones may drive changes occurring in the uterine microenvironment at term. Although there have been a number of studies considering the potential role(s) played by progesterone and estrogen at the time of parturition, the bio-availability and effects of androgens during pregnancy have received less scrutiny. The aim of this review is to highlight potential roles of androgens in the biology of pregnancy and parturition.METHODSA review of published literature was performed to address (i) androgen concentrations, including biosynthesis and clearance, in maternal and fetal compartments throughout gestation, (ii) associations of androgen concentrations with adverse pregnancy outcomes, (iii) the role of androgens in the physiology of cervical remodelling and finally (iv) the role of androgens in the physiology of myometrial function including any impact on contractility.RESULTSSome, but not all, androgens increase throughout gestation in maternal circulation. The effects of this increase are not fully understood; however, evidence suggests that increased androgens might regulate key processes during pregnancy and parturition. For example, androgens are believed to be critical for cervical remodelling at term, in particular cervical ripening, via regulation of cervical collagen fibril organization. Additionally, a number of studies highlight potential roles for androgens in myometrial relaxation via non-genomic, AR-independent pathways critical for the pregnancy reaching term. Understanding of the molecular events leading to myometrial relaxation is an important step towards development of novel targeted tocolytic drugs.CONCLUSIONSThe increase in androgen levels throughout gestation is likely to be important for establishment and maintenance of pregnancy and initiation of parturition. Further investigation of the underlying mechanisms of androgen action on cervical remodelling and myometrial contractility is needed. The insights gained may facilitate the development of new therapeutic approaches to manage pregnancy complications such as preterm birth.

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“…Both androstenedione and testosterone in the unconjugated form were shown to be elevated in PE vs normal pregnancy (Troisi et al 2003b), but were unchanged in cord blood serum. Others have also shown increased androgens in PE (Acromite et al 1999; Salamalekis et al 2006; Sharifzadeh et al 2012), and has been linked to dysregulation of p450 aromatase (Sathishkumar et al 2012; Steier et al 2002). Nonetheless, it is not clear how much this is a cause of PE and how much a consequence.…”

Section: Hormones Of Preeclampsia-related Endothelial Dysfunctionmentioning

confidence: 99%

Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

Boeldt

Bird

2017

Journal of Endocrinology

234

150

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Maternal vascular adaptation to pregnancy is critically important in order to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones with directly impact endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy but have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+ signaling events and chronically promoting the breakdown of endothelial cell-cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming more clear. We then describe in detail how the complex endocrine environment of PE effects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.

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A comparison of serum androgens in pre-eclamptic and normotensive pregnant women during the third trimester of pregnancy

Abstract: Serum androgen levels during third trimester of pregnancy are higher in pre-eclamptic women and this may propose an effect of androgens in the pathogenesis of pre-eclampsia.

Cited by 36 publications

References 15 publications

Testosterone Represses Estrogen Signaling by Upregulating miR-22

Testosterone Represses Estrogen Signaling by Upregulating miR-22

Androgens in pregnancy: roles in parturition

Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

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