Estrogen receptor (ESR) 2 partially offsets the absence of ESR1 in gonadotropes of pituitary-specific Esr1 knockout female mice

Estrogen receptor 1 and 2 (ESR1 and 2) mediate estrogen (E) action on gonadotrope function. While much is known about the effects of ESR1 on the gonadotrope, there is still some controversy regarding the effects of ESR2. To investigate the role of ESR2 in the gonadotrope, 45-day-old female mice of two different genotypes were used: wild type (WT) and pituitary (gonadotropes and thyrotropes)-specific Esr1 knockout (KO). All mice were ovariectomized (OVX) and 15 days later injected over 3 days with 2.5 μg 17β-estradiol (E2), 0.2 mg of the selective ESR1 or 2 agonists, propylpyrazole triol and diarylpropionitrile, respectively, or 0.1 ml oil. The day after treatment, anterior pituitary glands were dissected out for evaluation of gonadotrope ultrastructural morphology and pituitary immunohistochemical expression of progesterone receptor (Pgr (Pr)). Blood was collected and serum LH levels were assessed. Activation of ESR1 in WT mice resulted in the following: i) uterine ballooning and vaginal cornification, ii) negative feedback on LH secretion, iii) increased number of homogeneous (functional) gonadotropes, and iv) pituitary Pgr expression (35.9±2.0% of pituitary cells). Activation of ESR1 in KO mice induced normal uterine, vaginal, and LH secretion responses, but failed to increase the number of functional gonadotropes, and induced significantly lower Pgr expression (21.0±3.0% of pituitary cells) than in WT mice. Whilst activation of ESR2 had no significant effects in WT mice, it doubled the number of functional gonadotropes exhibited by KO mice injected with oil. It is concluded that E2 exerted its action in KO mouse gonadotropes via ESR2.

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Positive, But Not Negative Feedback Actions of Estradiol in Adult Female Mice Require Estrogen Receptor α in Kisspeptin Neurons

Endocrinology ◽

10.1210/en.2014-1851 ◽

2015 ◽

Vol 156 (3) ◽

pp. 1111-1120 ◽

Cited By ~ 77

Author(s):

Sharon L. Dubois ◽

Maricedes Acosta-Martínez ◽

Mary R. DeJoseph ◽

Andrew Wolfe ◽

Sally Radovick ◽

...

Keyword(s):

Estrogen Receptor ◽

Adult Female ◽

Negative Feedback ◽

Positive Feedback ◽

Estrogen Receptor Α ◽

Female Mice ◽

Lh Secretion ◽

Express Estrogen Receptor ◽

Specific Deletion

Abstract Hypothalamic kisspeptin (Kiss1) neurons express estrogen receptor α (ERα) and exert control over GnRH/LH secretion in female rodents. It has been proposed that estradiol (E2) activation of ERα in kisspeptin neurons in the arcuate nucleus (ARC) suppresses GnRH/LH secretion (negative feedback), whereas E2 activation of ERα in kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) mediates the release of preovulatory GnRH/LH surges (positive feedback). To test these hypotheses, we generated mice bearing kisspeptin cell–specific deletion of ERα (KERαKO) and treated them with E2 regimens that evoke either negative or positive feedback actions on GnRH/LH secretion. Using negative feedback regimens, as expected, E2 effectively suppressed LH levels in ovariectomized (OVX) wild-type (WT) mice to the levels seen in ovary-intact mice. Surprisingly, however, despite the fact that E2 regulation of Kiss1 mRNA expression was abrogated in both the ARC and AVPV of KERαKO mice, E2 also effectively decreased LH levels in OVX KERαKO mice to the levels seen in ovary-intact mice. Conversely, using a positive feedback regimen, E2 stimulated LH surges in WT mice, but had no effect in KERαKO mice. These experiments clearly demonstrate that ERα in kisspeptin neurons is required for the positive, but not negative feedback actions of E2 on GnRH/LH secretion in adult female mice. It remains to be determined whether the failure of KERαKO mice to exhibit GnRH/LH surges reflects the role of ERα in the development of kisspeptin neurons, in the active signaling processes leading to the release of GnRH/LH surges, or both.

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Pituitary Aromatase P450 May Be Involved in Maintenance of the Population of Luteinizing Hormone-Positive Pituitary Cells in Mice

Cells Tissues Organs ◽

10.1159/000445478 ◽

2016 ◽

Vol 201 (5) ◽

pp. 390-398 ◽

Cited By ~ 4

Author(s):

Jose Carretero ◽

Francisco López ◽

Leonardo Catalano-Iniesta ◽

Virginia Sanchez-Robledo ◽

Maria Jose Garcia-Barrado ◽

...

Keyword(s):

Luteinizing Hormone ◽

Pituitary Function ◽

Pituitary Cells ◽

Wild Type ◽

Female Mice ◽

Pathophysiological Role ◽

In The Wild ◽

17Β Estradiol ◽

Estradiol Synthesis

As aromatase P450 is located in several pituitary cells, testosterone can be transformed into 17β-estradiol in the gland by the enzyme. The possible role of this transformation in pituitary function remains to be elucidated, but some evidence suggests a physiological and pathophysiological role for pituitary aromatase. To determine its relevance in the modulation of pituitary function, mainly associated with reproduction, luteinizing hormone (LH)-positive cells in the hypophysis of female and male aromatase knockout (ArKO) mice were studied. In all LH-positive cells, significant increases in the cellular (p < 0.01) and nuclear (p < 0.05) areas were found in the ArKO mice compared to the wild-type mice. In the ArKO mice, LH-positive cells were more abundant (p < 0.01); they were characterized by a stronger cytoplasmic reaction and the cells were more polygonal and exhibited more short, thick cytoplasmic prolongations than those in the wild-type mice. Moreover, LH-positive cells showed a greater proliferation rate in the ArKO mice compared to the wild-type mice (p < 0.01). These findings suggest that the local production of estradiol mediated by pituitary aromatase is necessary for the regulation of LH-positive gonadotropic cells, exerting an autoparacrine inhibitory regulation. These results could underlie the higher pituitary aromatase expression observed in male versus female mice. Similar effects were found in ArKO male and female mice, suggesting that in both sexes the effects of estrogens on maintenance of the LH-positive pituitary cell population could be related to the local aromatization of testosterone to estradiol inside the hypophysis. Therefore, aromatase could modulate pituitary LH-positive cells in males through local estradiol synthesis.

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Pituitary Gonadotroph Estrogen Receptor-α Is Necessary for Fertility in Females

Endocrinology ◽

10.1210/en.2007-1084 ◽

2007 ◽

Vol 149 (1) ◽

pp. 20-27 ◽

Cited By ~ 47

Author(s):

Mary C. Gieske ◽

Hyun Joon Kim ◽

Sandra J. Legan ◽

Yongbum Koo ◽

Andree Krust ◽

...

Keyword(s):

Estrogen Receptor ◽

Estrogen Receptor Α ◽

Pituitary Cells ◽

Female Reproduction ◽

Estrogen Action ◽

Α Subunit ◽

Female Mice ◽

Reproductive Axis ◽

Serum Lh ◽

Estrous Cyclicity

Estrogens play a central role in regulating female reproduction throughout the reproductive axis, and the pituitary is one of the major targets of estrogen action. We hypothesized that estrogen receptor α (ERα) mediates estrogen action in the pituitary gonadotroph. To test this hypothesis, we generated a mouse line with a selective ERα deletion in the gonadotropin α-subunit (αGSU)-expressing pituitary cells (pituitary-specific ERα knockout; ERαflox/flox αGSUcre). Although the ERαflox/flox αGSUcre female mice maintain a basal level of serum LH and FSH and their ovulatory capacity is comparable to that in controls, they do not display regular estrous cycles and are infertile, indicating a potential disorder in regulating LH and/or FSH secretion. The ERαflox/flox αGSUcre female mice express equivalent levels of LHβ and αGSU mRNA compared with wild-type mice as determined by microarray analysis. Taken together, these findings indicate that pituitary gonadotroph ERα carries out the effects of estrogens with regard to estrous cyclicity and ultimately fertility.

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Pengaruh Pemberian Kedelai terhadap Sistem Reproduksi

Jurnal Penelitian Perawat Profesional ◽

10.37287/jppp.v1i1.18 ◽

2019 ◽

Vol 1 (1) ◽

pp. 53-60

Author(s):

Rizky Aprilia Wikayanti ◽

Andre Parmonangan Panjaitan

Keyword(s):

Menstrual Cycle ◽

Reproductive System ◽

Experimental Studies ◽

Review Literature ◽

Follicular Phase ◽

Free Concentration ◽

Human Reproductive ◽

17Β Estradiol ◽

Lh Secretion

Kedelai merupakan tanaman Leguminoceae, yang mengandung senyawa isoflavon. Struktur kimianya menyerupai 17β-estradiol yang memiliki kemampuan untuk berikatan dengan reseptor estrogen yang dapat berpengaruh terhadap sistem reproduksi manusia. Tujuan literatur review ini untuk mengetahui efek kedelai terhadap sistem reproduksi manusia. Metode yang digunakan adalah metode literatur review dari 50 artikel PubMed NCBI, Elsevier dan BMJ Journal yang diperoleh hanya 38 artikel yang digumakan dari tahun 2000 sampai dengan tahun 2018. Berbagai penelitian eksperimental yang dilakukan menunjukkan bahwa kedelai memiliki efek terhadap sistem reproduksi manusia. Kedelai dapat menyebabkan sekresi FSH, sekresi LH menurun dan meningkatkan konsentrasi estradiol bebas. Penurunan FSH dan LH dapat menyebabkan gangguan dalam siklus menstruasi terutama pada fase folikular dan ovulasi, jika fase folikular terganggu maka siklus menstruasi akan menjadi tidak teratur. Selain itu fitoestrogen yang terkandung dalam kedelai diketahui dapat menghambat 17-β hidroksisteroidoksidoreduktase sehingga mengakibatkan penurunan kadar testosteron. Kata kunci: kedelai, manusia, reproduksi THE ROLE OF SOYBEAN FOR REPRODUCTIVE SYSTEM ABSTRACT Soybean is a Leguminoceae plant, which contains isoflavone compounds. Its chemical structure resembles 17β-estradiol which has ability to bind to estrogen receptors which can affect the human reproductive system. The purpose of this review literature is to determine the effect of soy on the human reproductive system. Using research articles and books related to the effect of soy on the reproductive system from 2000 to 2018. Various experimental studies conducted showed that soy has an effect on the human reproductive system. Soy can cause FSH secretion, decreased LH secretion and increasing the free concentration of estradiol. Decreased FSH and LH can cause disruption in the menstrual cycle, especially in the follicular phase and ovulation, if the follicular phase is disrupted then the menstrual cycle will become irregular. In addition, phytoestrogens contained in soy are known to inhibit 17-β hydroxysteroidoxidoreductase, resulting in a decrease in testosterone levels. Keywords : human, reproductive, soybean

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Molecular mechanism of endocrine-disruptive effects induced by Bisphenol A: The role of transmembrane G-protein estrogen receptor 1 and integrin αvβ3

Journal of Environmental Sciences ◽

10.1016/j.jes.2018.05.002 ◽

2019 ◽

Vol 75 ◽

pp. 1-13 ◽

Cited By ~ 12

Author(s):

Zhiguo Sheng ◽

Cong Wang ◽

Furong Ren ◽

Yuxiang Liu ◽

Benzhan Zhu

Keyword(s):

Estrogen Receptor ◽

Bisphenol A ◽

G Protein ◽

Molecular Mechanism ◽

Integrin Αvβ3 ◽

Estrogen Receptor 1

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The role of oestrogens on gonadotrophin secretion in the testicular feminization syndrome1

Acta Endocrinologica ◽

10.1530/acta.0.0950314 ◽

1980 ◽

Vol 95 (3) ◽

pp. 314-318 ◽

Cited By ~ 3

Author(s):

Martha Medina ◽

Alfredo Ulloa-Aguirre ◽

Maria A. Fernández ◽

Gregorio Pérez-palacios

Keyword(s):

Clomiphene Citrate ◽

Poor Response ◽

Testicular Feminization ◽

Normal Response ◽

Serum Lh ◽

Gonadotrophin Secretion ◽

Before And After ◽

Complete Form ◽

Lh Secretion

Abstract. The role of oestrogens on gonadotrophin secretion was assessed in three related patients with the complete form of testicular feminization syndrome. Serum LH and FSH levels were measured before and after I.RH stimulation as well as before, during and after chronic clomiphene citrate administration. Moderately elevated LH basal levels with a significant LH rise following I.RH were observed. Normal or even low FSH level with poor response to LRH were found in all subjects. Administration of clomiphene citrate resulted in a significant serum LH increase without any change of FSH. Following castration both LH and FSH rose and a normal response to LRH was observed. These results were interpreted as demonstrating that, while endogenous oestrogens modulate LH secretion in patients with androgen unresponsiveness, it plays no role in regulating FSH secretion and suggested that a factor of testicular origin without androgenic or oestrogenic activity is responsible for FSH regulation.

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Adrenal progesterone facilitates the negative feedback of oestrogen on LH release in ovariectomized rats

Journal of Endocrinology ◽

10.1677/joe.0.1390253 ◽

1993 ◽

Vol 139 (2) ◽

pp. 253-258 ◽

Cited By ~ 7

Author(s):

A. M. Salicioni ◽

R. W. Carón ◽

R. P. Deis

Keyword(s):

Ovariectomized Rats ◽

Adrenal Steroids ◽

Serum Progesterone ◽

Oestrogen Treatment ◽

Ovx Rats ◽

Serum Lh ◽

Oestradiol Benzoate ◽

Lh Release ◽

Lh Secretion

ABSTRACT There is evidence that the adrenals play a role in the regulation of the synthesis and release of gonadotrophins in various vertebrates. The aim of this study was to determine the part played by adrenal steroids, with special reference to progesterone, on the concentration of LH in ovariectomized (OVX) and oestrogen-primed rats. OVX rats received a single s.c. injection of vehicle or oestradiol benzoate (OB, 20 μg/rat). This day was designated as day 0. Three or four days later (day 3–day 4), the rats were treated with mifepristone (10 mg/kg) or with two doses of progesterone antiserum and blood samples were obtained at 13.00 and 18.00 h. OB treatment of OVX rats reduced serum LH at 13.00 h and 18.00 h on day 3 but only at 13.00 h on day 4. The administration of mifepristone at 08.00 h to OVX and oestrogen-treated rats induced a significant increase in serum LH at 18.00 h on days 3 and 4, without modifying the values at 13.00 h. When mifepristone was given at 13.00 h a much larger increase in serum LH was obtained at 18.00 h. In OVX and oestrogen-treated rats, adrenalectomy on day 2 (08.00–09.00 h) induced an increase in serum LH at 18.00 h similar to that observed in the OVX and oestrogen-primed rats after mifepristone treatment. In order to determine the specificity of the effect of mifepristone, a group of OVX and oestrogentreated rats was injected with progesterone antiserum at 08.00 and 13.00 h on day 3. Serum LH concentrations at 13.00 and 18.00 h on day 3 were similar to values obtained in OVX rats treated with oestrogen and mifepristone. Serum progesterone was measured at 08.00 and 13.00 h in OVX and OVX and oestrogenprimed rats. At both times, values were similar in OVX rats but oestrogen treatment significantly increased serum progesterone levels. The important role of adrenal progesterone on the regulation of LH secretion in OVX and oestrogen-primed rats is evident from these results. Blocking progesterone action at the receptor level, we showed that OB significantly increased LH values at 18.00 h. On the basis of these studies it is tempting to speculate on the possibility of an inhibitory or stimulatory effect of oestrogen on serum LH concentration in OVX rats, according to the presence or absence of adrenal progesterone action. Journal of Endocrinology (1993) 139, 253–258

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G Protein-Coupled Estrogen Receptor 1 Regulates Human Neutrophil Functions

Biomedicine Hub ◽

10.1159/000454981 ◽

2017 ◽

Vol 2 (1) ◽

pp. 1-13 ◽

Cited By ~ 12

Author(s):

M. Carmen Rodenas ◽

Nicola Tamassia ◽

Isabel Cabas ◽

Federica Calzetti ◽

José Meseguer ◽

...

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Protein Kinase ◽

G Protein ◽

Respiratory Burst ◽

Human Neutrophils ◽

G Protein Coupled ◽

Estrogen Receptor 1

Background: The role of estrogens in immune functioning is relatively well known under both physiological and pathological conditions. Neutrophils are the most abundant circulating leukocytes in humans, and their abundance and function are regulated by estrogens, since they express estrogen receptors (ERs). Traditionally, estrogens were thought to act via classical nuclear ERs, namely ERα and ERβ. However, it was observed that some estrogens induced biological effects only minutes after their application. This rapid, “nongenomic” effect of estrogens is mediated by a membrane-anchored receptor called G protein-coupled estrogen receptor 1 (GPER1). Nevertheless, the expression and role of GPER1 in the immune system has not been exhaustively studied, and its relevance in neutrophil functions remains unknown. Methods: Human neutrophils were incubated in vitro with 10-100 µM of the GPER1-specific agonist G1 alone or in combination with lipopolysaccharide. GPER1 expression and subcellular localization, respiratory burst, life span, gene expression profile, and cell signaling pathways involved were then analyzed in stimulated neutrophils. Results: Human neutrophils express a functional GPER1 which regulates their functions through cAMP/protein kinase A/cAMP response element-binding protein, p38 mitogen-activated protein kinase, and extracellular regulated MAPK signaling pathways. Thus, GPER1 activation in vitro increases the respiratory burst of neutrophils, extends their life span, and drastically alters their gene expression proﬁle. Conclusions: Our results demonstrate that GPER1 activation promotes the polarization of human neutrophils towards a proinflammatory phenotype and point to GPER1 as a potential therapeutic target in immune diseases where neutrophils play a key role.

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