scholarly journals OR31-05 Emergence of Ovarian Hyperandrogenism and Luteal Insufficiency Following ESR1 Knockdown in the Mediobasal Hypothalamus of Adult Female Rhesus Monkeys

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jon E Levine ◽  
Emily P Greinwald ◽  
Jesi A Felton ◽  
Matthew T Flowers ◽  
Molly M Willging ◽  
...  
Keyword(s):  
Adult Female ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Mediobasal Hypothalamus ◽  
Serum Samples ◽  
Gadolinium Contrast ◽  
Menstrual Cycles ◽  
Female Rhesus ◽  
Luteal Insufficiency ◽  
Ovarian Hyperandrogenism

Abstract Diminished estradiol (E2) negative feedback action by neuronal ESR1 in the arcuate nucleus (ARC) of the mediobasal hypothalamus (MBH) is hypothesized to cause gonadotropin-releasing hormone (GnRH) hypersecretion, and thus LH excess, contributing to ovarian hyperandrogenism in polycystic ovary syndrome (PCOS). In primates, including humans, however, the mediating estrogen receptor is unknown. Thus, to test the hypothesis that diminished E2 action on ARC ESR1 contributes to female primate ovarian hyperandrogenism, eleven, ovary intact, adult female rhesus macaques, pair housed with female peers, received five 12µl MRI-guided MBH infusions into the rostral-to-caudal extent of both right and left ARC. Each infusion comprised gadolinium contrast agent and ~3-4 x 1010 adeno-associated virus 8 (AAV8) particles containing either a shRNA specific for ESR1 (n=6, ERaKD) or scrambled shRNA (n=5, control). Mid-surgery MRI scans identified targeting accuracy. 2-2.5 years following AAV8 infusion, EIA-determined P4 values were obtained from twice weekly serum samples; samples obtained during the follicular phase of menstrual cycles or anovulatory periods were submitted to liquid chromatography, tandem mass spectrometry (LCMS) for additional steroid hormones. LCMS-determined values were also obtained 0 hours (h) and 24 h following an IM injection of 200IU hCG. Both ERaKD (28.5 ± 1.3 days, mean ± SEM) and control (34.0 ± 3.3 days) female groups exhibited comparably regular menstrual cycles. ERaKD exhibited higher circulating levels of LH (2.8 ± 0.2 ng/ml, p=0.03), androstenedione (A4, 0.43 ± 0.03 ng/ml, p=0.03) and testosterone (T, 0.23 ± 0.03 ng/ml, p=0.09), and LH/FSH ratio (1.7 ± 0.2, p=0.05) compared to controls (LH, 2.1 ± 0.4; A4, 0.30 ± 0.05; T, 0.18 ± 0.01 ng/ml; LH/FSH 1.3 ± 0.2). Following an ovarian androgen-stimulating hCG injection, ERaKD 24-h peak levels for T (0.28 ± 0.01 ng/ml) were higher (p=0.03) compared to controls (0.21 ± 0.01 ng/ml). In addition, luteal insufficiency emerged in ERaKD females, with mean (2.4 ± 0.3 ng/ml), peak (3.6 ± 0.4 ng/ml) and area-under-the-curve (AUC, 23.2 ± 4.2 ng/ml/days) P4 values diminished compared to controls (mean, 3.6 ± 0.1, p=0.01; peak 5.7 ± 0.1 ng/ml, p=0.01; AUC, 43.7 ± 6.7 ng/ml/days, p=0.03). Taken together, these results suggest that knockdown of ARC ESR1 disrupts Gn stimulation of ovarian function, contributing to female monkey ovarian hyperandrogenism and menstrual cycle impairment emulating PCOS in women.

Reproductive endocrine effects of intranasal administration of progesterone to adult female rhesus monkeys

1985 ◽  
Vol 110 (4) ◽  
pp. 461-468 ◽  
Author(s):  
G. F. X. David ◽  
V. Puri ◽  
A. K. Dubey ◽  
C. P. Puri ◽  
T. C. Anand Kumar
Keyword(s):  
Menstrual Cycle ◽  
Phase Ii ◽  
Adult Female ◽  
Rhesus Monkeys ◽  
Intranasal Administration ◽  
Type I ◽  
Luteal Function ◽  
Menstrual Cycles ◽  
Female Rhesus ◽  
Endocrine Profile

Abstract. Adult female rhesus monkeys exhibiting normal ovulatory menstrual cycles were treated with progesterone nasal sprays. Animals in group A (n = 9) were treated with the solvent only (controls). Animals in groups B (n = 6), C (n = 17) and D (n = 7), respectively, were treated with a daily dose of 0.4, 2 and 10 μg of progesterone and the spraying was done between days 5–14 of the cycle. Ovulation was monitored by laparoscopy on day 20. The serum endocrine profile throughout the treated menstrual cycle was studied with respect to oestradiol and progesterone. Bioactive luteinizing hormone (bLH) was studied in blood samples taken on the day of the mid-cycle oestradiol peak, 2 days before, and 2 days after. The menstrual cycle was divided into two phases with respect to the mid-cycle oestradiol peak: phase I was taken to include day 1 of the cycle to the day of the oestradiol peak, and the remaining part of the menstrual cycle was considered to be phase II. The serum-endocrine profile in the controls was similar to that observed in normal ovulatory menstrual cycles. However, in the progesterone-treated groups three types of menstrual cycles were discernable on the basis of the serum endocrine profile. In the type I menstrual cycle, observed only in group C (n = 10), the mid-cycle bLH peak was abolished and the progesterone levels remained low throughout the cycle. Laparoscopy revealed these to be anovulatory cycles. In the type II menstrual cycle, seen in the 3 animals of group B, 2 animals of group C, and in all the 7 animals of group D, the mid-cycle bLH peak was abolished and the progesterone levels during phase II of the cycle were significantly lower than in the controls, indicative of poor luteal function. In the type III menstrual cycle seen in the remaining monkeys, the serum endocrine profile did not differ from that seen in the controls. Thus, the present studies indicate that the intranasal administration of progesterone shows a dose-response effect with respect to the suppression of the oestradiol induced mid-cycle surge of bLH. Suppression of the mid-cycle bLH peak resulted in anovulatory cycles or ovulatory cycles with poor luteal function.

Ovarian hyperandrogenism in adult female rhesus monkeys exposed to prenatal androgen excess

2002 ◽  
Vol 77 (1) ◽  
pp. 167-172 ◽  
Author(s):  
Joel R. Eisner ◽  
Melissa A. Barnett ◽  
Daniel A. Dumesic ◽  
David H. Abbott
Keyword(s):  
Adult Female ◽  
Rhesus Monkeys ◽  
Androgen Excess ◽  
Female Rhesus ◽  
Prenatal Androgen ◽  
Ovarian Hyperandrogenism

scholarly journals METABOLIC AND REPRODUCTIVE PCOS-LIKE TRAITS FOLLOWING ESR1 KNOCKDOWN IN THE MEDIOBASAL HYPOTHALAMUS OF ADULT FEMALE RHESUS MONKEYS

2020 ◽  
Vol 114 (3) ◽  
pp. e399
Author(s):  
David H. Abbott ◽  
Emily P. Greinwald ◽  
Jesi A. Felton ◽  
Matthew T. Flowers ◽  
Molly M. Willging ◽  
...  
Keyword(s):  
Adult Female ◽  
Rhesus Monkeys ◽  
Mediobasal Hypothalamus ◽  
Female Rhesus

Homoeopathic Management in a Case of Infertility with PCOS

2021 ◽  
Author(s):  
Padmalaya Rath ◽  
Shweta Gautam
Keyword(s):  
Ovarian Function ◽  
Polycystic Ovary ◽  
Sexually Active ◽  
Polycystic Ovaries ◽  
Ovary Syndrome ◽  
Menstrual Cycles ◽  
The Past ◽  
Irregular Menses ◽  
Anovulatory Infertility ◽  
Androgen Levels

AbstractInfertility is the inability of a sexually active couple, not using any birth control, to get pregnant after 1 year of trying. About one-quarter of female infertility is caused by a problem with ovulation. Polycystic ovary syndrome (PCOS) accounts for more than 75% of cases of anovulatory infertility. PCOS is a disorder of chronically abnormal ovarian function and hyperandrogenism (abnormally elevated androgen levels) manifested by irregular menstrual cycles, polycystic ovaries, excess unwanted hair, obesity etc. A case of a female aged 21 years with irregular menses for the past 2 years diagnosed with PCOS and inability to conceive has been reported here. The case was worked out as per homoeopathic principles and individualised homoeopathic medicine, Pulsatilla nigricans (Puls. nig.) was prescribed and the patient responded positively and conceived

scholarly journals SAT-587 Molecular Markers of Beige Adipose Following ESR1 Knockdown in the Mediobasal Hypothalamus of Adult Female Rhesus Monkeys

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sindhura Bandaru ◽  
Matthew T Flowers ◽  
Sona Perlin ◽  
Molly M Willging ◽  
Emily P Greinwald ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adult Female ◽  
Internal Control ◽  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Target Genes ◽  
Upper Body ◽  
Gadolinium Contrast ◽  
Beige Adipocytes ◽  
Female Rhesus

Abstract Our studies in female marmoset monkeys show that the ablation of ovarian estradiol (E2) production fails to alter energy homeostasis or body fat accumulation. Peripheral E2 may therefore not play a crucial role in metabolic regulation in female primates. shRNA-mediated knockdown of ESR1 expression in the hypothalamic ventromedial nucleus (VMN) in adult female rodents, however, induces obesity and suggests ESR1 is a hypothalamic target for E2 regulation of energy homeostasis, and likely mediates thermogenesis in brown/beige adipose depots. In female primates, including humans, the hypothalamic estrogen receptor mediating metabolic regulation is unknown. To test the hypothesis that ESR1 mediates female primate regulation of energy homeostasis, 11 ovary intact, adult female rhesus macaques, pair housed with female peers, received five 12µl MRI-guided MBH infusions into the rostral-to-caudal extent of both right and left VMN. Each infusion comprised a gadolinium contrast agent and ~3–4 x 1010 adeno-associated virus 8 (AAV8) particles containing either an shRNA specific for ESR1 (n=6, ERaKD) or scrambled shRNA (n=5, control). Mid-surgery MRI scans identified targeting accuracy. ~ 1.5 yrs following AAV8 infusion, pronounced gain in BMI enabled conversion of 83% of ERaKD females to overweight/obese compared to 20% of controls (p=0.08). Percent increase in BMI remained intermittently greater (p<0.05) than controls thereafter. Adipose depots were harvested at necropsy ~2.5–3 yrs following treatment. Total RNA was isolated using the Qiagen AllPrep DNA/RNA/miRNA Universal kit. RNA was reverse transcribed with High-Capacity cDNA Reverse Transcription kit (Applied Biosystems). All quantitative real-time PCR (qRT-PCR) were performed on a StepOnePlus System using Power SYBR Green master mix (Applied Biosystems). Primer sequences were designed using NCBI Primer-Blast. Expression of TATA-box binding protein (TBP) was used as the internal control housekeeping gene. The relative expression of target genes was measured using the comparative cycle threshold (Ct) method with results expressed as target mRNA expression relative to TBP using the formula 2^-delta Ct. Upper body beige adipose represents an organ system in primates, including humans, involved in thermogenesis. Axillary beige adipose depots in ERaKD females, however, did not exhibit significantly diminished gene expression for selected markers of beige adipocytes, including PAT2, CD137 and C/EBPβ, compared to control females. More crucially, thermogenically relevant UCP1 expression also did not differ between ERaKD females and controls. Taken together, these results suggest that knockdown of VMN ESR1 in adult female monkeys, while inducing modest weight gain after 1.5 years, may not markedly alter beige adipose gene expression of initially selected thermogenically relevant genes.

Light Exposure, Melatonin Secretion, and Menstrual Cycle Parameters: An Integrative Review

2007 ◽  
Vol 9 (1) ◽  
pp. 49-69 ◽  
Author(s):  
Mary Lee Barron
Keyword(s):  
Menstrual Cycle ◽  
Ovarian Function ◽  
Light Exposure ◽  
Polycystic Ovary ◽  
Menstrual Phase ◽  
Melatonin Secretion ◽  
Menstrual Cycles ◽  
Current State ◽  
Dark Exposure

Dysfunction in menstrual physiology has pronounced effects on quality of life, involving mood changes, body image, infertility, and pregnancy complications. Light exposure may affect menstrual cycles and symptoms through the influence of melatonin secretion. The purpose of this systematic review is to determine the current state of knowledge about the effects of light and melatonin secretion on menstrual phase and cycle alterations. A brief overview of the influence of melatonin on human physiology is included. There is evidence of a relationship between light exposure and melatonin secretion and irregular menstrual cycles, menstrual cycle symptoms, and disordered ovarian function. In women with a psychopathology such as bipolar disorder or an endocrinopathy such as polycystic ovary syndrome, there seems to be greater vulnerability to the influence of light—dark exposure. Research on the complex role of light—dark exposure in menstrual physiology has implications for treatment of menstrual-associated disorders.

scholarly journals Use of Inositols in Polycystic Ovary Syndrome

2020 ◽  
Vol 16 (28) ◽  
pp. 24-34
Author(s):  
O.A. Pustotina ◽  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
The Body ◽  
Metabolic Parameters ◽  
Ovary Syndrome ◽  
Pathogenetic Role

The article presents key data on the physiology of inositols in the body, their pathogenetic role in the development of polycystic ovary syndrome, and the possibilities of myo-inositol and D-chiro-inositol in the restoration of ovarian function, metabolic parameters, and overcoming of infertility.

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