Prenatal androgenization causes expression changes of progesterone and androgen receptor mRNAs in the arcuate nucleus of female mice across development

2021 ◽  
Author(s):  
Yugo Watanabe ◽  
Melanie Prescott ◽  
Rebecca E. Campbell ◽  
Christine L. Jasoni
Keyword(s):  
Androgen Receptor ◽  
Arcuate Nucleus ◽  
Female Mice ◽  
Receptor Mrnas

scholarly journals Subfertility in androgen-insensitive female mice is rescued by transgenic FSH

2017 ◽  
Vol 29 (7) ◽  
pp. 1426 ◽  
Author(s):  
K. A. Walters ◽  
M. C. Edwards ◽  
M. Jimenez ◽  
D. J. Handelsman ◽  
C. M. Allan
Keyword(s):  
Androgen Receptor ◽  
Litter Size ◽  
Ovarian Function ◽  
Reproductive Function ◽  
Antral Follicle ◽  
Female Fertility ◽  
Wild Type ◽  
Female Reproduction ◽  
Androgen Insensitivity ◽  
Female Mice

Androgens synergise with FSH in female reproduction but the nature of their interaction in ovarian function and fertility is not clear. In the present study, we investigated this interaction, notably whether higher endogenous FSH can overcome defective androgen actions in androgen receptor (AR)-knockout (ARKO) mice. We generated and investigated the reproductive function of mutant mice exhibiting AR resistance with or without expression of human transgenic FSH (Tg-FSH). On the background of inactivated AR signalling, which alone resulted in irregular oestrous cycles and reduced pups per litter, ovulation rates and antral follicle health, Tg-FSH expression restored follicle health, ovulation rates and litter size to wild-type levels. However, Tg-FSH was only able to partially rectify the abnormal oestrous cycles observed in ARKO females. Hence, elevated endogenous FSH rescued the intraovarian defects, and partially rescued the extraovarian defects due to androgen insensitivity. In addition, the observed increase in litter size in Tg-FSH females was not observed in the presence of AR signalling inactivation. In summary, the findings of the present study reveal that FSH can rescue impaired female fertility and ovarian function due to androgen insensitivity in female ARKO mice by maintaining follicle health and ovulation rates, and thereby optimal female fertility.

scholarly journals Sex Differences in Expression of Oestrogen Receptor α but not Androgen Receptor mRNAs in the Foetal Lamb Brain

2014 ◽  
Vol 26 (5) ◽  
pp. 321-328 ◽  
Author(s):  
R. C. Reddy ◽  
C. T. Estill ◽  
M. Meaker ◽  
F. Stormshak ◽  
C. E. Roselli
Keyword(s):  
Sex Differences ◽  
Androgen Receptor ◽  
Oestrogen Receptor ◽  
Oestrogen Receptor Α ◽  
Receptor Mrnas ◽  
Foetal Lamb

scholarly journals Inactivation of the androgen receptor in bone-forming cells leads to trabecular bone loss in adult female mice

2013 ◽  
Vol 2 ◽  
Author(s):  
Jorma A Määttä ◽  
Kalman G Büki ◽  
Kaisa K Ivaska ◽  
Vappu Nieminen-Pihala ◽  
Teresa D Elo ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Bone Loss ◽  
Trabecular Bone ◽  
Adult Female ◽  
Female Mice ◽  
Trabecular Bone Loss

Characterizing the neuroendocrine and ovarian defects of androgen receptor-knockout female mice

2013 ◽  
Vol 305 (6) ◽  
pp. E717-E726 ◽  
Author(s):  
Xiaobing B. Cheng ◽  
Mark Jimenez ◽  
Reena Desai ◽  
Linda J. Middleton ◽  
Shai R. Joseph ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Negative Feedback ◽  
Positive Feedback ◽  
Growth Patterns ◽  
Corpora Lutea ◽  
Preovulatory Follicle ◽  
Lh Surge ◽  
Antral Follicles ◽  
Female Mice ◽  
Follicle Diameter

Homozygous androgen receptor (AR)-knockout (ARKO) female mice are subfertile due to both intra- and extraovarian (neuroendocrine) defects as defined by ovary transplantation. Using ARKO mice, this study set out to reveal the precise AR-regulated pathways required for optimal androgen-regulated ovulation and fertility. ARKO females exhibit deficient neuroendocrine negative feedback, with a reduced serum luteinizing hormone (LH) response to ovariectomy (OVX) ( P < 0.01). Positive feedback is also altered as intact ARKO females, at late proestrus, exhibit an often mistimed endogenous ovulatory LH surge. Furthermore, at late proestrus, intact ARKO females display diminished preovulatory serum estradiol (E2; P < 0.01) and LH ( P < 0.05) surge levels and reduced Kiss1 mRNA expression in the anteroventral periventricular nucleus ( P < 0.01) compared with controls. However, this reduced ovulatory LH response in intact ARKO females can be rescued by OVX and E2 priming or treatment with endogenous GnRH. These findings reveal that AR regulates the negative feedback response to E2, E2-positive feedback is compromised in ARKO mice, and AR-regulated negative and positive steroidal feedback pathways impact on intrahypothalamic control of the kisspeptin/GnRH/LH cascade. In addition, intraovarian AR-regulated pathways controlling antral to preovulatory follicle dynamics are disrupted because adult ARKO ovaries collected at proestrus have small antral follicles with reduced oocyte/follicle diameter ratios ( P < 0.01) and increased proportions of unhealthy large antral follicles ( P < 0.05) compared with controls. As a consequence of aberrant follicular growth patterns, proestrus ARKO ovaries also exhibit fewer preovulatory follicle ( P < 0.05) and corpora lutea numbers ( P < 0.01). However, embryo development to the blastocyst stage is unchanged in ARKO females, and hence, the subfertility is a consequence of reduced ovulations and not altered embryo quality. These findings reveal that the AR has a functional role in neuroendocrine regulation and timing of the ovulatory LH surge as well as antral/preovulatory follicle development.

Sexually different actions of leptin in proopiomelanocortin neurons to regulate glucose homeostasis

2008 ◽  
Vol 294 (3) ◽  
pp. E630-E639 ◽  
Author(s):  
Haifei Shi ◽  
April D. Strader ◽  
Joyce E. Sorrell ◽  
James B. Chambers ◽  
Stephen C. Woods ◽  
...  
Keyword(s):  
Energy Balance ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Arcuate Nucleus ◽  
Fat Distribution ◽  
Male And Female ◽  
Female Mice ◽  
Leptin Receptors ◽  
Exogenous Glucose ◽  
Anorectic Effect

Leptin regulates energy balance and glucose homeostasis, at least in part, via activation of receptors in the arcuate nucleus of the hypothalamus located in proopiomelanocortin (POMC) neurons. Females have greater sensitivity to central leptin than males, suggested by a greater anorectic effect of central leptin administration in females. We hypothesized that the regulation of energy balance and peripheral glucose homeostasis of female rodents would be affected to a greater extent than in males if the action of leptin in POMC neurons were disturbed. Male and female mice lacking leptin receptors only in POMC neurons gained significantly more body weight and accumulated more body fat. However, female mice gained disproportionately more visceral adiposity than males, and this appeared to be largely the result of differences in energy expenditure. When maintained on a high-fat diet (HFD), both male and female mutants had higher levels of insulin following exogenous glucose challenges. Chow- and HFD-fed males but not females had abnormal glucose disappearance curves following insulin administrations. Collectively, these data indicate that the action of leptin in POMC neurons is sexually different to influence the regulation of energy balance, fat distribution, and glucose homeostasis.

294 ACCELERATED ATHEROSCLEROSIS IN FEMALE MICE LACKING THE ANDROGEN RECEPTOR

2011 ◽  
Vol 12 (1) ◽  
pp. 64
Author(s):  
J. Bourghardt ◽  
A. Wilhelmson ◽  
C. Alexanderson ◽  
K. De Gendt ◽  
G. Verhoeven ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Accelerated Atherosclerosis ◽  
Female Mice

scholarly journals Female Mice Haploinsufficient for an Inactivated Androgen Receptor (AR) Exhibit Age-Dependent Defects That Resemble the AR Null Phenotype of Dysfunctional Late Follicle Development, Ovulation, and Fertility

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3674-3684 ◽  
Author(s):  
K. A. Walters ◽  
C. M. Allan ◽  
M. Jimenez ◽  
P. R. Lim ◽  
R. A. Davey ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Ovarian Function ◽  
Gene Dosage ◽  
Early Embryo ◽  
Ovulation Rate ◽  
Corpora Lutea ◽  
Cell Stage ◽  
Gene Dosage Effect ◽  
Female Mice ◽  
Age Dependent

The role of classical genomic androgen receptor (AR) mediated actions in female reproductive physiology remains unclear. Female mice homozygous for an in-frame deletion of exon 3 of the Ar (AR−/−) were subfertile, exhibiting delayed production of their first litter (AR+/+ = 22 d vs. AR−/− = 61 d, P &lt; 0.05) and producing 60% fewer pups/litter (AR+/+: 8.1 ± 0.4 vs. AR−/−: 3.2 ± 0.9, P &lt; 0.01). Heterozygous females (AR+/−) exhibited an age-dependent 55% reduction (P &lt; 0.01) in pups per litter, evident from 6 months of age (P &lt; 0.05), compared with AR+/+, indicating a significant gene dosage effect on female fertility. Ovulation was defective with a significant reduction in corpora lutea numbers (48–79%, P &lt; 0.01) in 10- to 12- and 26-wk-old AR+/− and AR−/− females and a 57% reduction in oocytes recovered from naturally mated AR−/− females (AR+/+: 9.8 ± 1.0 vs. AR−/−: 4.2 ± 1.2, P &lt; 0.01); however, early embryo development to the two-cell stage was unaltered. The delay in first litter, reduction in natural ovulation rate, and aromatase expression in AR+/− and AR−/− ovaries, coupled with the restored ovulation rate by gonadotropin hyperstimulation in AR−/− females, suggest aberrant gonadotropin regulation. A 2.7-fold increase (AR+/+: 35.4 ± 13.4 vs. AR−/−: 93.9 ± 6.1, P &lt; 0.01) in morphologically unhealthy antral follicles demonstrated deficiencies in late follicular development, although growing follicle populations and growth rates were unaltered. This novel model reveals that classical genomic AR action is critical for normal ovarian function, although not for follicle depletion and that haploinsufficiency for an inactivated AR may contribute to a premature reduction in female fecundity.

scholarly journals Postnatal Overnutrition Induces Changes in Synaptic Transmission to Leptin Receptor-Expressing Neurons in the Arcuate Nucleus of Female Mice

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2425
Author(s):  
Thais Tessari Zampieri ◽  
Tabata Mariz Bohlen ◽  
Marina Augusto Silveira ◽  
Larissa Campista Lana ◽  
Daniella G. de Paula ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Neural Plasticity ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Postnatal Period ◽  
Pubertal Stage ◽  
Female Mice ◽  
Expression Of Genes ◽  
Cellular Excitability ◽  
Modulation Of Gene Expression

The adipocyte-derived hormone leptin is a potent neurotrophic factor that contributes to the neural plasticity and development of feeding circuitry, particularly in the arcuate nucleus of the hypothalamus (ARH). Postnatal overnutrition affects leptin secretion and sensitivity, but whether postnatal overnutrition produces changes in the development of the synaptic transmission to ARH neurons is currently unknown. We evaluated the excitatory and inhibitory currents to ARH leptin receptor (LepR)-expressing neurons in prepubertal, pubertal and adult female mice. The effects of postnatal overnutrition in the expression of genes that code ion channels subunits in the ARH were also evaluated. We observed that the transition from prepubertal to pubertal stage is characterized by a rise in both excitatory and inhibitory transmission to ARH LepR-expressing neurons in control mice. Postnatal overnutrition induces a further increase in the excitatory synaptic transmission in pubertal and adult animals, whereas the amplitude of inhibitory currents to ARH LepR-expressing cells was reduced. Postnatal overnutrition also contributes to the modulation of gene expression of N-methyl-D-aspartate, GABAB and ATP-sensitive potassium channel subunits in ARH. In summary, the synaptic transmission to ARH cells is profoundly influenced by postnatal overnutrition. Thus, increased adiposity during early postnatal period induces long-lasting effects on ARH cellular excitability.

Androgen Receptor is Expressed in Murine Choroid Plexus and Downregulated by 5α-Dihydrotestosterone in Male and Female Mice

2008 ◽  
Vol 38 (1) ◽  
pp. 41-49 ◽  
Author(s):  
C. Henrique Alves ◽  
Isabel Gonçalves ◽  
Sílvia Socorro ◽  
Graça Baltazar ◽  
Telma Quintela ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Choroid Plexus ◽  
Male And Female ◽  
Female Mice
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