scholarly journals 158. Effects of phytoestrogens on the ovarian and pituitary phenotypes of oestrogen deficient female aromatase knockout mice

2004 ◽  
Vol 16 (9) ◽  
pp. 158
Author(s):  
K. L. Britt ◽  
E. R. Simpson ◽  
J. K. Findlay
Keyword(s):  
Sertoli Cells ◽  
Hormone Replacement ◽  
Reproductive Organ ◽  
Treatment Regimes ◽  
Reproductive Axis ◽  
Ovarian Morphology ◽  
Subunit Expression ◽  
Synthetic Estrogens ◽  
Serum Gonadotropin

Phytoestrogens can induce both estrogen agonistic and antagonistic effects, depending on the tissue, estrogen receptor content and endogenous levels of estrogen. Dietary phytoestrogens are promoted as alternatives to synthetic estrogens for hormone replacement therapy, however their effects on the reproductive axis have not been exhaustively studied in vivo. Female aromatase knockout mouse (ArKO) mice are estrogen-free, and anovulatory with a block in folliculogenesis, hemorrhagic cysts and development of Sertoli cells within their ovaries. We evaluated the ArKO mouse as a model to test the effects of phytoestrogen-supplemented diets on the reproductive organ weights, ovarian morphology, gonadotropin levels and the transcript levels of ovarian somatic cell and steroidogenic markers. The extent to which phytoestrogens either as soyfree or soymeal diet or genistein added to a soyfree diet, exert estrogenic effects varied with the type of phytoestrogen and the parameter being tested. The genistein diet significantly increased uterine and ovarian weights of ArKO compared to wildtype mice, whilst both the soy, and to a larger extent the genistein diet, improved ovarian morphology compared to the soyfree diet. Transformation to morphological Sertoli cells in ArKO mice was decreased by both phytoestrogen diets, whilst the gene expression of Sertoli cell markers was not affected. The soy diet increased both LH and FSH in both genotypes compared to animals on the soyfree diet. The genistein diet reduced FSH levels in ArKO mice, correlating with increased ovarian inhibin subunit expression. In conclusion, phytoestrogens are estrogenic in ArKO mice. Specifically, they can affect serum gonadotropin levels, and offset the development of Sertoli cells and hemorrhagic cysts within the ovaries, depending on the type of dietary phytoestrogen. Further studies are required to determine the effective doses and treatment regimes for phytoestrogens as endocrine modulators. Supported by NH&MRC Reg Key#198705.

scholarly journals Impairments in the reproductive axis of female mice lacking estrogen receptor β in GnRH neurons

2018 ◽  
Vol 315 (5) ◽  
pp. E1019-E1033 ◽  
Author(s):  
Horacio J. Novaira ◽  
Ariel L. Negron ◽  
Jones B. Graceli ◽  
Silvia Capellino ◽  
Andrew Schoeffield ◽  
...  
Keyword(s):  
Mouse Models ◽  
Reproductive Function ◽  
Stimulation Test ◽  
Abnormal Development ◽  
Gnrh Neuron ◽  
Serum Luteinizing Hormone ◽  
Reproductive Axis ◽  
Gnrh Neurons ◽  
Serum Gonadotropin

The effect of estrogen on the differentiation and maintenance of reproductive tissues is mediated by two nuclear estrogen receptors (ERs), ERα, and ERβ. Lack of functional ERα and ERβ genes in vivo significantly affects reproductive function; however, the target tissues and signaling pathways in the hypothalamus are not clearly defined. Here, we describe the generation and reproductive characterization of a complete-ERβ KO (CERβKO) and a GnRH neuron-specific ERβKO (GERβKO) mouse models. Both ERβKO mouse models displayed a delay in vaginal opening and first estrus. Hypothalamic gonadotropin-releasing hormone (GnRH) mRNA expression levels in both ERβKO mice were similar to control mice; however female CERβKO and GERβKO mice had lower basal and surge serum gonadotropin levels. Although a GnRH stimulation test in both female ERβKO models showed preserved gonadotropic function in the same animals, a kisspeptin stimulation test revealed an attenuated response by GnRH neurons, suggesting a role for ERβ in normal GnRH neuron function. No alteration in estrogen-negative feedback was observed in either ERβKO mouse models after ovariectomy and estrogen replacement. Further, abnormal development of ovarian follicles with low serum estradiol levels and impairment of fertility were observed in both ERβKO mouse models. In male ERβKO mice, no differences in the timing of pubertal onset or serum luteinizing hormone and follicle-stimulating hormone levels were observed as compared with controls. Taken together, these data provide in vivo evidence for a role of ERβ in GnRH neurons in modulating puberty and reproduction, specifically through kisspeptin responsiveness in the female hypothalamic-pituitary-gonadal axis.

scholarly journals Cardiovascular disease and osteoporosis: is there a link between lipids and bone?

2002 ◽  
Vol 39 (3) ◽  
pp. 203-210 ◽  
Author(s):  
John R Burnett ◽  
Samuel D Vasikaran
Keyword(s):  
Cardiovascular Disease ◽  
Bone Density ◽  
Vascular Calcification ◽  
Cholesterol Biosynthesis ◽  
Hormone Replacement ◽  
Plasma Lipid ◽  
Clinical Effects ◽  
Cardiovascular Morbidity And Mortality ◽  
The Relationship

Atherosclerotic heart disease and osteoporosis are both diseases of old age. Evidence is accumulating for a link between vascular and bone disease. Calcification is a common feature of atherosclerotic plaques, and osteoporosis is associated with both atherosclerosis and vascular calcification. However, the relationship of vascular calcification to the pathogenesis of atherosclerosis remains incompletely understood. Hormone replacement therapy has beneficial effects in the prevention of both atherosclerosis and osteoporosis. Bisphosphonates inhibit bone resorption and are used in the treatment of osteoporosis, whereas the statins inhibit cholesterol biosynthesis and are used for the treatment of atherosclerosis. We have reviewed recent advances in the knowledge of the actions of bisphosphonates and statins at the cellular, molecular and end-organ levels in order to examine the relationship between cardiovascular disease and osteoporosis and to explore the link between lipids and bones. These studies suggest that the mechanism of actions of these two classes of drugs at the cellular level may not be mutually exclusive. There are some early clinical data to complement these findings, suggesting that statins increase bone density and bisphosphonates may have a beneficial effect in vivo on plasma lipid levels and on the atherosclerotic process. Properly designed prospective studies that examine the effect of statins on bone density and fractures, as well as the effects of bisphosphonates on lipid profiles, atherosclerotic progression and cardiovascular morbidity and mortality are needed to define clearly the clinical effects and potential new roles for these agents.

scholarly journals Ezrin is an Actin Binding Protein That Regulates Sertoli Cell and Spermatid Adhesion During Spermatogenesis

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3981-3995 ◽  
Author(s):  
N. Ece Gungor-Ordueri ◽  
Elizabeth I. Tang ◽  
Ciler Celik-Ozenci ◽  
C. Yan Cheng
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Adherens Junction ◽  
Actin Binding ◽  
Permeability Barrier ◽  
Tight Junction Permeability ◽  
Residual Bodies ◽  
Cell Interface

Abstract During spermatogenesis, the transport of spermatids and the release of sperms at spermiation and the remodeling of the blood-testis barrier (BTB) in the seminiferous epithelium of rat testes require rapid reorganization of the actin-based cytoskeleton. However, the mechanism(s) and the regulatory molecule(s) remain unexplored. Herein we report findings that unfold the functional significance of ezrin in the organization of the testis-specific adherens junction at the spermatid-Sertoli cell interface called apical ectoplasmic specialization (ES) in the adluminal compartment and the Sertoli cell-cell interface known as basal ES at the BTB. Ezrin is expressed at the basal ES/BTB in all stages, except from late VIII to IX, of the epithelial cycle. Its knockdown by RNA interference (RNAi) in vitro perturbs the Sertoli cell tight junction-permeability barrier via a disruption of the actin microfilaments in Sertoli cells, which in turn impeded basal ES protein (eg, N-cadherin) distribution, perturbing the BTB function. These findings were confirmed by a knockdown study in vivo. However, the expression of ezrin at the apical ES is restricted to stage VIII of the cycle and limited only between step 19 spermatids and Sertoli cells. A knockdown of ezrin in vivo by RNAi was found to impede spermatid transport, causing defects in spermiation in which spermatids were embedded deep inside the epithelium, and associated with a loss of spermatid polarity. Also, ezrin was associated with residual bodies and phagosomes, and its knockdown by RNAi in the testis also impeded the transport of residual bodies/phagosomes from the apical to the basal compartment. In summary, ezrin is involved in regulating actin microfilament organization at the ES in rat testes.

scholarly journals The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm

2020 ◽  
Vol 10 (6) ◽  
pp. 335 ◽  
Author(s):  
Mieko Oka ◽  
Isao Ono ◽  
Kampei Shimizu ◽  
Mika Kushamae ◽  
Haruka Miyata ◽  
...  
Keyword(s):  
Shear Stress ◽  
Intracranial Aneurysms ◽  
Hormone Replacement ◽  
Inflammatory Cells ◽  
Female Rats ◽  
Vasa Vasorum ◽  
Epidemiological Evidence ◽  
Bilateral Ovariectomy ◽  
The Poor

Considering the poor outcome of subarachnoid hemorrhage (SAH) due to the rupture of intracranial aneurysms (IA), mechanisms underlying the pathogenesis of IAs, especially the rupture of lesions, should be clarified. In the present study, a rat model of IAs in which induced lesions spontaneously ruptured resulting in SAH was used. In this model, the combination of the female sex and the bilateral ovariectomy increased the incidence of SAH, similar to epidemiological evidence in human cases. Importantly, unruptured IA lesions induced in female animals with bilateral ovariectomy were histopathologically similar to ruptured ones in the presence of vasa vasorum and the accumulation of abundant inflammatory cells, suggesting the exacerbation of the disease. The post-stenotic dilatation of the carotid artery was disturbed by the bilateral ovariectomy in female rats, which was restored by hormone replacement therapy. The in vivo study thus suggested the protective effect of estrogen from the ovary on endothelial cells loaded by wall shear stress. β-estradiol or dihydrotestosterone also suppressed the lipopolysaccharide-induced expression of pro-inflammatory genes in cultured macrophages and neutrophils. The results of the present study have thus provided new insights about the process regulating the progression of the disease.

Effects of Tokishakuyakusan, Keishibukuryogan, Shakuyakukanzoto and Unkeito on Ovarian Endothelin, Renin and Angiotensin II in Pregnant Mare's Serum Gonadotropin-treated Immature Rats

1992 ◽  
Vol 20 (02) ◽  
pp. 175-179 ◽  
Author(s):  
Satoshi Usuki ◽  
Yoshie Usuki ◽  
Junko Tanaka ◽  
Yuko Kawakura
Keyword(s):  
Angiotensin Ii ◽  
Herbal Medicines ◽  
Renin Angiotensin System ◽  
Concomitant Treatment ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Immature Rats ◽  
Serum Gonadotropin ◽  
Peptide System

We have previously proposed the ovarian ERAANPS (endothelin-renin-angiotensin-atrial natriuretic peptide system). The present study was undertaken to examine in vivo the effects of herbal medicines [Tokishakuyakusan (TS), Keishibukuryogan (KB), Shakuyakukanzoto (SK) and Unkeito (UT)] on endothelin-l (ET), renin and angiotensin II (A II) in the ovaries, of immature rats treated with 10 IU PMS for 48 h. ET and all components of renin-angiotensin system (RAS) were found at high levels in the ovary. Concomitant treatment with PMS plus TS, KB, SK or UT, especially TS and UT, tended to decrease the ET levels in ovary, while components of RAS tended to increase. However, ET, renin and A II levels in plasma were not at all affected after treatment with TS, KB, SK or UT. These results suggest that TS, KB, SK or UT may regulate the ovarian ERAANPS.

Thyroid hormone modulates androgen and oestrogen receptor content in the Sertoli cells of peripubertal rats

1996 ◽  
Vol 148 (1) ◽  
pp. 43-50 ◽  
Author(s):  
M L Panno ◽  
D Sisci ◽  
M Salerno ◽  
M Lanzino ◽  
V Pezzi ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Oestrogen Receptor ◽  
Age Groups ◽  
Strong Relationship ◽  
Inhibitory Influence ◽  
Aromatase Activity ◽  
Severe Impairment ◽  
Cellular Compartments

Abstract A possible role of tri-iodothyronine (T3) on the interplay between testicular steroids and Sertoli cells has been investigated on the basis of previous findings demonstrating a direct inhibitory influence of T3 on aromatase activity and oestradiol production in peripuberal Sertoli cells. In this context, the present study was focused on the effects of T3 on oestrogen receptor (ER) and androgen receptor (AR) contents in the cytosol and nucleus of Sertoli cells isolated from 2-, 3- and 4-week-old euthyroid, hypothyroid and hypothyroid treated rats. Hypothyroidism was induced by the oral administration of 0·025% methimazole (MMI) from birth until the rats were killed at 2, 3 and 4 weeks of age. Half of the MMI-treated animals were injected i.p. with l-tri-iodothyronine (T3; 3 μg/100 g body weight) during the last week before death. Sertoli cells from all groups were initially cultured under basal conditions for the first 24 h and subsequently in the presence of testosterone with or without T3 for an additional 24 h. Hypothyroidism was associated with severe impairment of body as well as testicular growth. Euthyroid ERs showed an elevated Kd (0·76 nm) which was similar in the different age groups investigated. The in vitro addition of T3 or testosterone induced a decrease in ER content and this decrease was greater after exposure to both hormones. In 2- and 3-week-old hypothyroid rats, ER content was markedly increased and was reversed in euthyroid rats when T3 was given in vivo. When ERs were assayed in the Sertoli cell nucleus and cytoplasm of 2- and 3-week-old animals, a strong relationship in ER content in the two cellular compartments was observed. Neither of the hormones tested seemed to affect the AR content in the nucleus significantly, while the in vitro addition of testosterone or T3 or both hormones together augmented the ARs in the cytosol to a greater extent, resulting in an increase in their total (cytosolic and nuclear) content in the cells. The present data suggest that T3 down-regulates ERs and up-regulates ARs in peripuberal Sertoli cells. The additive effect of testosterone and T3 in up-regulating ARs could possibly involve a role for T3 in influencing the androgen responsiveness of the Sertoli cells during spermatogenesis. Journal of Endocrinology (1996) 148, 43–50

scholarly journals Irisin in the primate hypothalamus and its effect on GnRH in vitro

2019 ◽  
Vol 241 (3) ◽  
pp. 175-187 ◽  
Author(s):  
Fazal Wahab ◽  
Ikram Ullah Khan ◽  
Ignacio Rodriguez Polo ◽  
Hira Zubair ◽  
Charis Drummer ◽  
...  
Keyword(s):  
Rhesus Monkeys ◽  
Peroxisome Proliferator ◽  
Developmentally Regulated ◽  
Peroxisome Proliferator Activated Receptor ◽  
Reproductive Effects ◽  
Reproductive Axis ◽  
Hypothalamic Cells ◽  
Endocrine Factor

Irisin, encoded by the FNDC5 gene, is a recently discovered endocrine factor mainly secreted as a myokine and adipokine. However, irisin/FNDC5 expression has also been reported in different other organs including components of the reproductive axis. Yet, there is the scarcity of data on FNDC5/irisin expression, regulation and its reproductive effects, particularly in primates. Here, we report the expression of FNDC5/irisin, along with PGC1A (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and ERRA (estrogen-related receptor alpha), in components of the reproductive axis of marmoset monkeys. Hypothalamic FNDC5 and ERRA transcript levels are developmentally regulated in both male and female. We further uncovered sex-specific differences in FNDC5, ERRA and PGC1A expression in muscle and the reproductive axis. Moreover, irisin and ERRα co-localize in the marmoset hypothalamus. Additionally, in the arcuate nucleus of rhesus monkeys, the number of irisin+ cells was significantly increased in short-term fasted monkeys as compared to ad libitum-fed monkeys. More importantly, we observed putative interaction of irisin-immunoreactive fibers and few GnRH-immunoreactive cell bodies in the mediobasal hypothalamus of the rhesus monkeys. Functionally, we noted a stimulatory effect of irisin on GnRH synthesis and release in mouse hypothalamic neuronal GT1-7 cells. In summary, our findings show that FNDC5 and irisin are developmentally, metabolic-status dependently and sex-specifically expressed in the primate hypothalamic–pituitary–gonadal axis and exert a stimulatory effect on GnRH expression and release in mouse hypothalamic cells. Further studies are required to confirm the reproductive effects of irisin in vivo and to illuminate the mechanisms of its regulation.

scholarly journals Cell-type specific analysis of physiological action of estrogen in mouse oviducts

2020 ◽  
Author(s):  
Emily A. McGlade ◽  
Gerardo G. Herrera ◽  
Kalli K. Stephens ◽  
Sierra L. W. Olsen ◽  
Sarayut Winuthayanon ◽  
...  
Keyword(s):  
Hormone Replacement ◽  
Cell Types ◽  
Normal Embryo ◽  
Developmental Defect ◽  
Cell Type ◽  
Specific Analysis ◽  
Cell Type Specific ◽  
17Β Estradiol ◽  
Oviductal Cell

AbstractOne of the endogenous estrogens, 17β-estradiol (E2) is a female steroid hormone secreted from the ovary. It is well established that E2 causes biochemical and histological changes in the uterus. The oviduct response to E2 is virtually unknown in an in vivo environment. In this study, we assessed the effect of E2 on each oviductal cell type, using an ovariectomized-hormone-replacement mouse model, single cell RNA-sequencing (scRNA-seq), in situ hybridization, and cell-type-specific deletion in mice. We found that each cell type in the oviduct responded to E2 distinctively, especially ciliated and secretory epithelial cells. The treatment of exogenous E2 did not drastically alter the transcriptomic profile from that of endogenous E2 produced during estrus. Moreover, we have identified and validated genes of interest in our datasets that may be used as cell- and region-specific markers in the oviduct. Insulin-like growth factor 1 (Igf1) was characterized as an E2-target gene in the mouse oviduct and was also expressed in human Fallopian tubes. Deletion of Igf1 in progesterone receptor (Pgr)-expressing cells resulted in female subfertility, partially due to an embryo developmental defect and embryo retention within the oviduct. In summary, we have shown that oviductal cell types are differentially regulated by E2 and support gene expression changes that are required for normal embryo development and transport in mouse models.

GABAA Receptor–Mediated Miniature Postsynaptic Currents and α-Subunit Expression in Developing Cortical Neurons

1999 ◽  
Vol 82 (6) ◽  
pp. 3286-3297 ◽  
Author(s):  
D. D. Dunning ◽  
C. L. Hoover ◽  
I. Soltesz ◽  
M. A. Smith ◽  
D. K. O'Dowd
Keyword(s):  
Synaptic Transmission ◽  
Decay Time ◽  
Cortical Neurons ◽  
Pcr Analysis ◽  
Decay Kinetics ◽  
Newborn Mice ◽  
Α Subunit ◽  
Postsynaptic Currents ◽  
Subunit Expression

Previous studies have described maturational changes in GABAergic inhibitory synaptic transmission in the rodent somatosensory cortex during the early postnatal period. To determine whether alterations in the functional properties of synaptically localized GABAAreceptors (GABAARs) contribute to development of inhibitory transmission, we used the whole cell recording technique to examine GABAergic miniature postsynaptic currents (mPSCs) in developing cortical neurons. Neurons harvested from somatosensory cortices of newborn mice showed a progressive, eightfold increase in GABAergic mPSC frequency during the first 4 wk of development in dissociated cell culture. A twofold decrease in the decay time of the GABAergic mPSCs, between 1 and 4 wk, demonstrates a functional change in the properties of GABAARs mediating synaptic transmission in cortical neurons during development in culture. A similar maturational profile observed in GABAergic mPSC frequency and decay time in cortical neurons developing in vivo (assessed in slices), suggests that these changes in synaptically localized GABAARs contribute to development of inhibition in the rodent neocortex. Pharmacological and reverse transcription-polymerase chain reaction (RT-PCR) studies were conducted to determine whether changes in subunit expression might contribute to the observed developmental alterations in synaptic GABAARs. Zolpidem (300 nM), a subunit-selective benzodiazepine agonist with high affinity for α1-subunits, caused a reversible slowing of the mPSC decay kinetics in cultured cortical neurons. Development was characterized by an increase in the potency of zolpidem in modulating the mPSC decay, suggesting a maturational increase in percentage of functionally active GABAARs containing α1 subunits. The relative expression of α1 versus α5 GABAAR subunit mRNA in cortical tissue, both in vivo and in vitro, also increased during this same period. Furthermore, single-cell RT-multiplex PCR analysis revealed more rapidly decaying mPSCs in individual neurons in which α1 versus α5 mRNA was amplified. Together these data suggest that changes in α-subunit composition of GABAARs contribute to the maturation of GABAergic mPSCs mediating inhibition in developing cortical neurons.

scholarly journals Gonadotrope-specific deletion of the BMP type 2 receptor does not affect reproductive physiology in mice†‡

2019 ◽  
Vol 102 (3) ◽  
pp. 639-646 ◽  
Author(s):  
Luisina Ongaro ◽  
Xiang Zhou ◽  
Yiming Cui ◽  
Ulrich Boehm ◽  
Daniel J Bernard
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Reproductive Organ ◽  
Conditional Knockout ◽  
Type Ii ◽  
Loss Of Function ◽  
Estrous Cyclicity ◽  
Transcription In Vitro

Abstract Activins selectively stimulate follicle-stimulating hormone (FSH) secretion by pituitary gonadotrope cells. More recently, other members of the TGFbeta superfamily, the bone morphogenetic proteins (BMPs), were reported to regulate FSH synthesis. Activins and BMPs independently and synergistically stimulate transcription of the FSHbeta subunit (Fshb) gene in immortalized gonadotrope-like cells. Both ligands can signal via the activin receptor type IIA (ACVR2A) to regulate FSH synthesis in vitro. In vivo, global Acvr2a knockout mice exhibit a 60% reduction in circulating FSH relative to wild-type animals, suggesting that activins, BMPs, or related ligands might signal through additional type II receptors to regulate FSH in vivo. Although the leading candidates are ACVR2B and the BMP type II receptor (BMPR2), only the latter mediates activin or BMP2 induction of Fshb transcription in vitro. Here, we generated mice carrying a loss of function mutation in Bmpr2 specifically in gonadotropes. Puberty onset, estrous cyclicity, and reproductive organ weights were similar between control and conditional knockout females. Serum FSH and luteinizing hormone (LH) and pituitary expression of Fshb and the LHbeta subunit (Lhb) were similarly unaffected by the gene deletion in both sexes. These results suggest that BMPR2 might not play a necessary role in FSH synthesis or secretion in vivo or that another type II receptor, such as ACVR2A, can fully compensate for its absence. These data also further contribute to the emerging concept that BMPs may not be physiological regulators of FSH in vivo.

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