Oestrogenic action of neonatal tamoxifen on the hypothalamus and reproductive system in female mice

2017 ◽  
Vol 29 (5) ◽  
pp. 1012 ◽  
Author(s):  
Rahmatollah Parandin ◽  
Morteza Behnam-Rassouli ◽  
Nasser Mahdavi-Shahri
Keyword(s):  
Reproductive System ◽  
Reproductive Function ◽  
Female Mice ◽  
Treatment And Prevention ◽  
Receptor Modulator ◽  
Neuron Populations ◽  
Reproductive Axis ◽  
First Time ◽  
The Brain ◽  
Selective Oestrogen Receptor Modulator

Tamoxifen, a selective oestrogen receptor modulator, is widely used for both the treatment and prevention of breast cancer in women; however, it is known to have adverse effects in the female reproductive system. Growing evidence suggests that oestrogen-sensitive neuron populations of the anteroventral periventricular (AVPV) nucleus and arcuate (ARC) nucleus, especially kisspeptin neurons, play a pivotal role in the timing of puberty onset and reproductive function. The aim of the present study was to evaluate whether neonatal exposure to tamoxifen affects oestrogenic actions in the brain and reproductive function in mice. On 1 to 5 postnatal days, female pups were injected subcutaneously with sesame oil (sham), oestradiol benzoate (EB; 20 µg kg–1), tamoxifen (0.4 mg kg–1) or EB+tamoxifen. Control mice received no treatment. Mice in the EB, tamoxifen and tamoxifen+EB groups exhibited advanced vaginal opening, disrupted oestrous cycles and a decreased follicular pool. Conversely, in these groups, there was a reduction in kisspeptin (Kiss1) mRNA expression, the neuronal density of AVPV and ARC nuclei and LH and oestradiol concentrations in the serum. The results of the present study confirm oestrogenic actions of tamoxifen in the brain and reproductive system. In addition, we show, for the first time, that tamoxifen has oestrogenic effects on the oestrogen-sensitive hypothalamic AVPV and ARC nuclei controlling the reproductive axis in female mice.

Differential role of melanocortins in mediating leptin's central effects on feeding and reproduction

2000 ◽  
Vol 278 (1) ◽  
pp. R50-R59 ◽  
Author(s):  
John G. Hohmann ◽  
Thomas H. Teal ◽  
Donald K. Clifton ◽  
James Davis ◽  
Victor J. Hruby ◽  
...  
Keyword(s):  
Food Intake ◽  
Reproductive System ◽  
Melanocortin Receptor ◽  
Reproductive Axis ◽  
The Status ◽  
Reproductive Endocrine ◽  
Intracerebroventricular Injections ◽  
Ingestive Behaviors ◽  
The Brain

Leptin serves as a humoral link coupling the status of energy reserves to the functional activity of the reproductive system. Leptin is thought to act through melanocortinergic pathways in the brain to regulate ingestive behaviors; however, whether melanocortins mediate leptin's actions on the neuroendocrine-reproductive axis is unknown. We tested this hypothesis first by determining whether the effects of leptin on feeding behavior and reproduction in the ob/ob mouse could be blocked by the melanocortin receptor (MC-R) antagonist SHU9119 and second, by examining the effects of the MC-R agonist MTII on feeding and the endocrine-reproductive system. Administered by intracerebroventricular injections, leptin inhibited food intake, raised plasma gonadotropin levels, and increased seminal vesicle weights compared with controls; SHU9119 (intracerebroventricularly) attenuated leptin's effects on food intake and body weight but did not alter leptin's stimulatory effect on the reproductive axis. MTII (intracerebroventricularly and intraperitoneally) decreased food intake and increased body temperature compared with controls but had no effect on the reproductive-endocrine axis. These results suggest that although leptin acts centrally through melanocortinergic pathways to inhibit ingestive behaviors and stimulate metabolism, leptin's activational effect on the reproductive axis is likely to be mediated by other, unknown neuroendocrine circuits.

scholarly journals Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose

2020 ◽  
Vol 105 (5) ◽  
pp. 1538-1551
Author(s):  
Angela Delaney ◽  
Rita Volochayev ◽  
Brooke Meader ◽  
Janice Lee ◽  
Konstantinia Almpani ◽  
...  
Keyword(s):  
Reproductive Function ◽  
Normal Breast ◽  
Breast Development ◽  
Reproductive Axis ◽  
Gnrh Neurons ◽  
Male Patients ◽  
And Function ◽  
Human Embryology ◽  
The Brain ◽  
Insight Into

Abstract Context The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. Objective The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. Methods We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. Results All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. Conclusions Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.

scholarly journals Hypothalamic pathways linking energy balance and reproduction

2008 ◽  
Vol 294 (5) ◽  
pp. E827-E832 ◽  
Author(s):  
Jennifer W. Hill ◽  
Joel K. Elmquist ◽  
Carol F. Elias
Keyword(s):  
Energy Balance ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Arcuate Nucleus ◽  
Metabolic Stress ◽  
Reproductive Function ◽  
Reproductive Axis ◽  
Hypothalamic Nuclei ◽  
Adiposity Signals ◽  
The Brain

During periods of metabolic stress, animals must channel energy toward survival and away from processes such as reproduction. The reproductive axis, therefore, has the capacity to respond to changing levels of metabolic cues. The cellular and molecular mechanisms that link energy balance and reproduction, as well as the brain sites mediating this function, are still not well understood. This review focuses on the best characterized of the adiposity signals: leptin and insulin. We examine their reproductive role acting on the classic metabolic pathways of the arcuate nucleus, NPY/AgRP and POMC/CART neurons, and the newly identified kisspeptin network. In addition, other hypothalamic nuclei that may play a role in linking metabolic state and reproductive function are discussed. The nature of the interplay between these elements of the metabolic and reproductive systems presents a fascinating puzzle, whose pieces are just beginning to fall into place.

scholarly journals Long-term consequences of surgical treatment of ovarian apoplexy

2021 ◽  
Vol 4 ◽  
pp. 93-98
Author(s):  
O.M. Ishak
Keyword(s):  
Risk Factors ◽  
Surgical Treatment ◽  
Postoperative Period ◽  
Reproductive System ◽  
Reproductive Function ◽  
Natural Resistance ◽  
Treatment And Prevention ◽  
Long Term Consequences

The objective: to determine the long-term consequences of surgical treatment of ovarian apoplexy, taking into account the risk factors of this urgent pathology.Materials and methods. The study included 112 women (main group, n=112), who underwent surgery for ovarian apoplexy, and 40 patients in the control group (n=40), who had no history of this pathology. All patients underwent a comprehensive examination using clinical, instrumental and laboratory research methods. The groups were homogeneous in age (mean age was 23,6±4,2) and statistically comparable.Results. Based on the analysis of clinical and anamnestic data of patients who underwent surgical treatment of ovarian apoplexy, we identified the main risk factors for this pathology: chronic diseases of the urinary, respiratory and digestive systems, genital infantilism, ovarian retention cysts, chronic salpingo-oophoritis, , menstrual disorders by type of hyperpolymenorrhea and/or algodysmenorrhea, family thrombophilic history, bleeding of various localizations in the anamnesis, artificial abortions, weight loss, smoking.Our proposed comprehensive two-stage rehabilitation system included treatment and prevention measures from the acute period of ovarian apoplexy to the time of reproductive function. The first stage of the treatment complex (early postoperative period) helped to eliminate the effects of ovarian injury, pain relief and hypercoagulable changes in the blood coagulation system, improving the quality of life during inpatient treatment. The second stage (2 months after surgery) provided the restoration of ovarian function and balance of the hemostasis system, thus preparing a woman’s reproductive system for future pregnancy and childbirth. In the remote postoperative period, the complex stage of rehabilitation in 23 treated patients resulted in the birth of healthy children and the absence of obstetric complications in 22 of them.Conclusion. Identification and structuring of risk factors for ovarian apoplexy is an important step for comprehensive treatment and prevention of recurrence of this disease. Eliminating or reducing the impact of these factors will help restore the reproductive system and improve quality of life.A comprehensive assessment of the state of the whole organism in the remote postoperative period indicates the need for rehabilitation measures aimed at increasing the natural resistance of the macroorganism and the effective restoration of reproductive function.

Effects of fluoxetine on the reproductive axis of female goldfish (Carassius auratus)

2008 ◽  
Vol 35 (3) ◽  
pp. 273-282 ◽  
Author(s):  
Jan A. Mennigen ◽  
Christopher J. Martyniuk ◽  
Kate Crump ◽  
Huiling Xiong ◽  
E. Zhao ◽  
...  
Keyword(s):  
Reproductive Function ◽  
Goldfish Carassius Auratus ◽  
Fluoxetine Treatment ◽  
Reproductive Axis ◽  
Dopaminergic Pathway ◽  
Plasma Estradiol ◽  
Potential Link ◽  
And Behavior ◽  
The Brain ◽  
Serotonergic Modulation

We investigated the effects of fluoxetine, a selective serotonin reuptake inhibitor, on neuroendocrine function and the reproductive axis in female goldfish. Fish were given intraperitoneal injections of fluoxetine twice a week for 14 days, resulting in five injections of 5 μg fluoxetine/g body wt. We measured the monoamine neurotransmitters serotonin, dopamine, and norepinephrine in addition to their metabolites with HPLC. Homovanillic acid, a metabolite in the dopaminergic pathway, increased significantly in the hypothalamus. Plasma estradiol levels were measured by radioimmunoassay and were significantly reduced approximately threefold after fluoxetine treatment. We found that fluoxetine also significantly reduced the expression of estrogen receptor (ER)β1 mRNA by 4-fold in both the hypothalamus and the telencephalon and ERα mRNA by 1.7-fold in the telencephalon. Fluoxetine had no effect on the expression of ERβ2 mRNA in the hypothalamus or telencephalon. Microarray analysis identified isotocin, a neuropeptide that stimulates reproductive behavior in fish, as a candidate gene affected by fluoxetine treatment. Real-time RT-PCR verified that isotocin mRNA was downregulated approximately sixfold in the hypothalamus and fivefold in the telencephalon. Intraperitoneal injection of isotocin (1 μg/g) increased plasma estradiol, providing a potential link between changes in isotocin gene expression and decreased circulating estrogen in fluoxetine-injected fish. Our results reveal targets of serotonergic modulation in the neuroendocrine brain and indicate that fluoxetine has the potential to affect sex hormones and modulate genes involved in reproductive function and behavior in the brain of female goldfish. We discuss these findings in the context of endocrine disruption because fluoxetine has been detected in the environment.

Regulators and Integration of Peripheral Signals

2021 ◽  
Author(s):  
Michelle T. Foster
Keyword(s):  
Adipose Tissue ◽  
Reproductive Function ◽  
Energy Regulation ◽  
Energy Status ◽  
Peripheral Tissues ◽  
Reproductive Axis ◽  
Reproductive Events ◽  
Ovarian Cyclicity ◽  
Reproductive Processes ◽  
The Brain

In mammals, reproductive function is closely regulated by energy availability. It is influenced by both extremes of nutrition, too few calories (undernutrition) and an excessive amount of calories (obesity). Atypical decreases or increases in weight can have adverse effects on the reproductive axis. This includes suppression of reproductive function, decreases in ovarian cyclicity, reduction in fertility, anovulation, and dysregulation of spermatogenesis. The balance between energy regulation and reproduction is supervised by a complex system comprised of the brain and peripheral tissues. The brain senses and integrates various systemic and central signals that are indicative of changes in body physiology and energy status. This occurs via numerous factors, including metabolic hormones and nutrients. Adipokines, endocrine factors primarily secreted by white adipose tissue, and adipose tissue related cytokines (adipocytokines) contribute to the regulation of maturity, fertility, and reproduction. Indeed, some adipokines play a fundamental role in reproductive disorders. The brain, predominantly the hypothalamus, is responsible for linking adipose-derived signals to pathways controlling reproductive processes. Gonadotropin-releasing hormone (GnRH) cells in the hypothalamus are fundamental in relaying adipose-derived signals to the pituitary–gonadal axis, which consequently controls reproductive processes. Leptin, adiponectin, apelin, chermin, resistin, and visfatin are adipokines that regulate reproductive events via the brain.

Effects of ageing and exogenous melatonin on pituitary responsiveness to GnRH in rats

Reproduction ◽  
2000 ◽  
pp. 151-156 ◽  
Author(s):  
E Diaz ◽  
D Pazo ◽  
AI Esquifino ◽  
B Diaz
Keyword(s):  
Body Weight ◽  
Reproductive System ◽  
Plasma Concentrations ◽  
Pituitary Hormones ◽  
Female Rats ◽  
Control Groups ◽  
Melatonin Treatment ◽  
Exogenous Melatonin ◽  
Reproductive Axis ◽  
Effect Of Age

The effect of age and melatonin on the activity of the neuroendocrine reproductive system was studied in young cyclic (3-5 months-old), and old acyclic (23-25 month-old) female rats. Pituitary responsiveness to a bolus of GnRH (50 ng per 100 g body weight) was assessed at both reproductive stages in control and melatonin-treated (150 micrograms melatonin per 100 g body weight each day for 1 month) groups. After this experiment, female rats were treated for another month to study the influence of ageing and melatonin on the reproductive axis. Plasma LH, FSH, prolactin, oestradiol and progesterone were measured. A positive LH response to GnRH was observed in both control groups (cyclic and acyclic). However, a response of greater magnitude was observed in old acyclic rats. Melatonin treatment reduced this increased response in acyclic rats and produced a pituitary responsiveness similar to that of young cyclic rats. FSH secretion was independent of GnRH administration in all groups, indicating desynchronization between LH and FSH secretion in response to GnRH in young animals and during senescence. No effect on prolactin was observed. Significantly higher LH (3009.11 +/- 1275.08 pg ml(-1); P < 0.05) and FSH concentrations (5879.28 +/- 1631.68 pg ml(-1); P < 0.01) were seen in acyclic control rats. After melatonin treatment, LH (811.11 +/- 89.71 pg ml(-1)) and FSH concentrations (2070 +/- 301.62 pg ml(-1)) decreased to amounts similar to those observed in young cyclic rats. However, plasma concentrations of oestradiol and progesterone were not reduced. In conclusion, the results of the present study indicate that, during ageing, the effect of melatonin is exerted primarily at the hypothalamo-pituitary axis rather than on the ovary. Melatonin restored the basal concentrations of pituitary hormones and pituitary responsiveness to similar values to those observed in young rats.

Chaperonin as the normal controls and pathological anti-stress response in the human reproductive system

2016 ◽  
pp. 126-129
Author(s):  
M. Makarenko ◽  
◽  
D. Hovsyeyev ◽  
L. Sydoryk ◽  
◽  
...  
Keyword(s):  
Reproductive System ◽  
Stress Proteins ◽  
Physiological Stress ◽  
Protein Complexes ◽  
Reproductive Function ◽  
Intercellular Signaling ◽  
Toll Like Receptors ◽  
Wide Range ◽  
Protein Functions ◽  
And Function

Different kinds of physiological stress cause mass changes in the cells, including the changes in the structure and function of the protein complexes and in separate molecules. The protein functions is determined by its folding (the spatial conclusion), which depends on the functioning of proteins of thermal shock- molecular chaperons (HSPs) or depends on the stress proteins, that are high-conservative; specialized proteins that are responsible for the correct proteinaceous folding. The family of the molecular chaperones/ chaperonins/ Hsp60 has a special place due to the its unique properties of activating the signaling cascades through the system of Toll-like receptors; it also stimulates the cells to produce anti- inflammatory cytokines, defensins, molecules of cell adhesion and the molecules of MHC; it functions as the intercellular signaling molecule. The pathological role of Hsp60 is established in a wide range of illnesses, from diabetes to atherosclerosis, where Hsp60 takes part in the regulation of both apoptosis and the autoimmune processes. The presence of the HSPs was found in different tissues that are related to the reproductive system. Key words: molecular chaperons (HSPs), Toll-like receptors, reproductive function, natural auto antibody.

Development of innovative hygienic technologies for preservation of the workers’ reproductive health

2020 ◽  
pp. 792-792
Author(s):  
M. A. Fesenko ◽  
G. V. Golovaneva ◽  
A. V. Miskevich
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Reproductive Health ◽  
Reproductive System ◽  
Preventive Measures ◽  
Learning Algorithms ◽  
Reproductive Function ◽  
Machine Learning Algorithms ◽  
New Model

The new model «Prognosis of men’ reproductive function disorders» was developed. The machine learning algorithms (artificial intelligence) was used for this purpose, the model has high prognosis accuracy. The aim of the model applying is prioritize diagnostic and preventive measures to minimize reproductive system diseases complications and preserve workers’ health and efficiency.

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