scholarly journals erbB-1 and erbB-4 Receptors Act in Concert to Facilitate Female Sexual Development and Mature Reproductive Function

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1465-1472 ◽  
Author(s):  
Vincent Prevot ◽  
Alejandro Lomniczi ◽  
Gabriel Corfas ◽  
Sergio R. Ojeda

Glial erbB-1 and erbB-4 receptors are key components of the process by which neuroendocrine glial cells control LHRH secretion and the onset of female puberty. We now provide evidence that these two signaling systems work in a coordinated fashion to control reproductive function. To generate animals carrying functionally impaired erbB-1 and erbB-4 receptors, we crossed Waved 2 (Wa-2+/+) mice harboring a point mutation of the erbB-1 receptor with mice expressing a dominant-negative erbB-4 receptor in astrocytes. In comparison to single-deficient mice, double-mutant animals exhibited a further delay in the onset of puberty and a strikingly diminished adult reproductive capacity. Ligand-dependent erbB receptor phosphorylation and erbB-mediated MAPK (ERK 1/2) phosphorylation were impaired in mutant astrocytes. Wa-2+/+ or double-mutant astrocytes failed to respond to TGFα with production of prostaglandin E2, one of the factors mediating the stimulatory effect of astroglial erbB receptor activation on LHRH release. Medium conditioned by Wa-2+/+ or double-mutant astrocytes treated with TGFα failed to stimulate LHRH release from GT1–7 cells. The LH response to ovariectomy was significantly attenuated in mutant mice in comparison with wild-type controls. Although the Wa-2 mutation affects all cells bearing erbB-1 receptors, these results suggest that a major defect underlying the reproductive defects of animals with impaired erbB signaling is a decreased ability of glial cells to stimulate LHRH release. Thus, a coordinated involvement of erbB-1 and erbB-4 signaling systems is required for the normalcy of sexual development and the maintenance of mature female reproductive function.

2017 ◽  
Vol 217 (1) ◽  
pp. 93-106 ◽  
Author(s):  
Nicole M. Templeman ◽  
Coleen T. Murphy

Nutrients are necessary for life, as they are a crucial requirement for biological processes including reproduction, somatic growth, and tissue maintenance. Therefore, signaling systems involved in detecting and interpreting nutrient or energy levels—most notably, the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway, mechanistic target of rapamycin (mTOR), and adenosine monophosphate-activated protein kinase (AMPK)—play important roles in regulating physiological decisions to reproduce, grow, and age. In this review, we discuss the connections between reproductive senescence and somatic aging and give an overview of the involvement of nutrient-sensing pathways in controlling both reproductive function and lifespan. Although the molecular mechanisms that affect these processes can be influenced by distinct tissue-, temporal-, and pathway-specific signaling events, the progression of reproductive aging and somatic aging is systemically coordinated by integrated nutrient-sensing signaling pathways regulating somatic tissue maintenance in conjunction with reproductive capacity.


Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2364-2376 ◽  
Author(s):  
Ursula S. Sandau ◽  
Alison E. Mungenast ◽  
Zefora Alderman ◽  
S. Pablo Sardi ◽  
Adam I. Fogel ◽  
...  

Female sexual maturation requires erythroblastosis B (erbB)4 signaling in hypothalamic astrocytes; however, the mechanisms by which erbB4 contributes to this process are incompletely understood. Here we show that SynCAM1, a synaptic adhesion molecule with signaling capabilities, is not only expressed highly in neurons, but also in hypothalamic astrocytes and is functionally associated with erbB4 receptor activity. Whereas SynCAM1 expression is diminished in astrocytes with impaired erbB4 signaling, ligand-dependent activation of astroglial erbB4 receptors results in rapid association of erbB4 with SynCAM1 and activation of SynCAM1 gene transcription. To determine whether astrocytic SynCAM1-dependent intracellular signaling is required for normal female reproductive function, we generated transgenic mice that express in an astrocyte-specific manner a dominant-negative form of SynCAM1 lacking the intracellular domain. The mutant protein was correctly targeted to the cell membrane and was functionally viable as shown by its ability to block intracellular calcium/calmodulin-dependent serine protein kinase redistribution, a major SynCAM1-mediated event. Dominant-negative-SynCAM1 female mice had a delayed onset of puberty, disrupted estrous cyclicity, and reduced fecundity. These deficits were associated with a reduced capacity of neuregulin-dependent erbB4 receptor activation to elicit prostaglandin E2 release from astrocytes and GnRH release from the hypothalamus. We conclude that one of the mechanisms underlying erbB4 receptor-mediated facilitation of glial-neuronal interactions in the neuroendocrine brain involves SynCAM1-dependent signaling and that this interaction is required for normal female reproductive function.


2018 ◽  
Vol 56 ◽  
pp. 136-140
Author(s):  
G. S. Sharapa ◽  
O. V. Boyko

Scientific and production experiments were carried out on cows of Ukrainian Black-and-White diary breed (UBAWD) of SE "Seagull" (branch "Lisne") during 2016–2017. The anatomical and physiological state of genital organs of cows was determined by the method of clinical and gynecological research of animals before conducting experiments and during them every 40–50 days. In total 486 cows were kept under control, which were kept in typical rooms with running platforms, but the active motivation of animals was clearly insufficient. Feeding cows according to the recommended standards. The milk yield from the cow in 2017 was 7813 kg. The experiments studied the effect of feeding cows during the dry period, the conditions of retention and some other paratypic factors on the course of the genera and the postnatal period, the duration of the service period and the fertility of cows. In analyzing the research results, personal records and veterinary documentation were used. In conducting experiments, it was found that normal calving was in 89% of cows, and severe and pathological – in 11% of cases. The main diseases in the afterlife period were: detention of the litter – 9.5%, postpartum endometritis – 21.5%, hypofunction of the ovaries – 23.0%, persistent yellow ovarian bodies – 25.6% and others. Normal intervals between stages of excitation of the sexual cycle (18–22 days) were in 63% of cows, and violations of the rhythm of sexual cycle, associated with dysfunction of the ovaries and missed the hunt – 30% of animals. Subunvulation of the genital organs of the cows contributed to the diseases of the limbs, udder and digestive disorders. During 2016–2017, the effect of feeding cows (173 g.) in the dry period on the course of calving, post-autumn period and their fertility was studied. Under the same conditions, keeping cows in the maternity ward and feeding rough and succulent feeds concentrated feeds fed cows of the control group (98 heads) to 1–2 kg daily during the dry period, and experimental (75 heads) – for 18–20 days to calving 2–3 kg. A positive difference was found in favor of cows of the experimental group: there was a more active stage of expulsion of the fetus, less delay of the placenta (by 7%) and endometritis (by 12%), the duration of the postoperative regenerative period decreased by 8.6 days; service period – 19.0 days; fertility from two inseminans was higher by 5.7%. Study of the reproductive capacity of cows at the hotel in different seasons showed that the recovery period was shorter by 11 days in the presence of cows in 3–4 quarters, and the service period – by 23.2 days at hotel in I and IV sq. The average duration of the recovery period was 79.5 days, while the service period was 123.4 days. The longest duration of the joint ventricle was in cows at hotel during the hot summer days of the year. The average fertilization rate from the first insemination of 339 cows was 44.9% with fluctuations in individual groups of milkers from 26.8% to 55.0%. The following indicators were in the number 1 and number 3 (respectively 26.8% and 31.4%). The best fertility rates were in groups № 4, 6 and 7, where there were more cows of the second and third lactation, and the responsible attitude of the milkers to work in organizing cows walks and sexually explicit hunting. When comparing the assessment of the duration of the IP and SP in full-age cows and cows, the first-born, taking into account 225 goals. It was found that these indicators were longer in primitive cows – 20.7 days respectively and 21.9 days in relation to full-age cows. The obtained results are completely consistent with the results obtained by a number of both domestic and foreign researchers. More attention is needed to grow heifers and to prepare newborns for delivery. In 15–17% of cows at and after the hotel, gynecological diseases that occurred in the presence of gastrointestinal diseases, lameness, mastitis and others were diagnosed. This has negatively affected the overall performance of the herd. In studying the duration of HP and SP in healthy and sick cows after calving, it was found that if the SP in healthy cows lasts 73.4 days, then in patients – 116.3 days (the difference was 42.9 days), and the difference in the duration of the joint venture reached 98.7 days. On the basis of the results of the research, it can be concluded that the reproductive function of the cows is influenced by such paratypic factors as feeding animals in the dry period, the temperature factor (time of year), the human factor (the effect of milking on a group of cows), age and physiological state of cows in the hotel and in the afterlife period. When feeding 2–3 kg of bovine feed for cows, together with rough and juicy fodder for 18–20 days prior to calving, the recovery period decreased by 8.6 days and service period – by 19 days, and fertility from two inseminals increased by 5.7%, reaching 85.3%. The smallest duration of the service-period was in the presence of cows in the I and IV quarters year (107.7–117.1 days). In primary cows, the recovery period was longer than that of full-age cows by 20.7 days, and the service period was 21.9 days. In the physiologically healthy cows after calving, the recovery period lasted an average of 73.4 days and service period – 98.7 days, and in patients, after the prescribed treatment – respectively 116.3 days and 197.4 days.


2021 ◽  
Vol 11 (2) ◽  
pp. 157-169
Author(s):  
Pavlo Skliarov ◽  
Serhiy Fedorenko ◽  
Svitlana Naumenko ◽  
Oleksandr Onyshchenko ◽  
Alina Pasternak ◽  
...  

Animal reproduction is one of the main factors limiting the efficiency of livestock production. Its optimal level is possibly achieved when certain conditions are created for animals. As reproduction is a complex reflex process depending on neuroendocrine regulatory mechanisms, the character and strength of stimuli, which, in turn, is due to a number of factors. Under normal conditions, the body of animals is affected by many different factors, which are appropriately transformed and specified by positive or negative reactions. Inhibitory factors include air pool, saturated with harmful substances and gases, ionizing radiation, poor water quality along with altered redox properties, hypokinesia combined with poor unbalanced feeding, systematic chronic stress, presence of toxic substances in feed, and the deficiency of vitamins and other bioantioxidants in feed or their excessive spending. Of the wide range of genetic and paratypic factors of negative impacts on reproductive capacity, the most common one is alimentary, which causes impaired reproductive function due to deficiencies in the rules, regulations, and feeding regime of animals. In particular, the alimentary can be associated with both general malnutrition (starvation) and overfeeding (obesity). However, the alimentary form of infertility mostly occurs due to low-quality diets when the diet lacks vital components (mainly vitamins, macro-, and micronutrients) or the quantitative ratios of the ingredients are violated. This is possible even if the total nutritional value of the diet meets the established requirements for the physiological needs of the body. Vitamins, micro-, and macronutrients are ecologically deficient factors of disturbance of animal reproductive function, the influence of which is observed on all processes of reproduction, from fertilization to the postpartum period and the preservation of young animals. The pathogenesis of their insufficiency is associated with the violation of steroido-, gameto-, and embryogenesis and the emergence of ante-, intra-, neo- and postnatal pathologies, respectively. Therefore, treatments and prevention measures should be aimed at providing animals with biologically complete balanced feeding and replenishment of the body with vitamins and minerals. However, all these issues remain incompletely studied and need further research.


Author(s):  
Mikhail S. Shelygin ◽  
Nadezhda S. Guziy ◽  
Viktoria S. Kaplitskaya

The combined dyshormonal pathology of the uterus and mammary glands represents a great danger to the health of a woman, as well as impairs the quality of life, reduces the reproductive capacity of a woman and leads to premature loss of reproductive function. Steroid hormones play a large role in the regulation of proliferative changes in the uterus and mammary glands. Regulation of target organs, uterus and mammary glands, due to the presence of common mechanisms associated with the presence of the receptor apparatus in the tissues of these organs to sex hormones. The general links of pathogenesis and the high frequency of combined pathology of the uterus and mammary glands are of interest to study not only isolated forms of proliferation, but also the development of a unified systematic approach to the study of this pathology. In recent times, there are opposing views on the role of hormonal dysfunction as a factor in proliferative processes. The management tactics of patients with pathological changes in the mammary gland in various gynecological diseases is an assessment of endocrine status, normalization of hormonal and metabolic disorders, especially when progesterone and cortisol are excreted, testosterone levels are increased, and hyperprolactinemia is affected. Special attention should be paid to patients with menstrual disorders, reproductive health disorders. We believe that the problem of the hyperproliferative processes of the uterus and mammary glands should not be considered only from the perspective of gynecological or mammological practice. This pathology is polymorphic and should have broad interdisciplinary connections with such disciplines as oncology, endocrinology, gastroenterology, psychiatry, therapy, pathomorphology, histology, obstetrics and gynecology. Only by studying all possible links of etiopathogenesis, by combining interdisciplinary communication, it is possible to effectively fight for the quality of patients with a combined pathology of the uterus and mammary glands. Family planning, prevention of unplanned pregnancy, timely implementation of maternity, prevention of miscarriage, the use of modern contraceptives, support for breastfeeding is also of high importance for the prevention of disorders and the preservation, extension of reproductive capabilities, and the prevention of combined dyshormonal pathology of the uterus and breast.


1997 ◽  
Vol 110 (18) ◽  
pp. 2215-2225 ◽  
Author(s):  
J.C. Guillemot ◽  
P. Montcourrier ◽  
E. Vivier ◽  
J. Davoust ◽  
P. Chavrier

Engagement of the high affinity IgE receptor (FcepsilonRI) in mast cells elicits a series of intracellular signalling events including cytoskeletal reorganization and granule exocytosis. To analyze the coupling of receptor activation to specific cytoskeletal responses, we expressed dominant negative mutant forms of the Rho GTPases CDC42 and Rac1 in rat RBL-2H3 tumor mast cells. We show here that dominant inhibition of CDC42 function decreases cell adhesion, interferes with Fc(epsilon)RI-induced actin plaque assembly and reduced the recruitment of vinculin at the cell-substratum interface, while the inhibitory Rac1 mutant abolishes Fc(epsilon)RI-mediated membrane ruffling. The expression of trans-dominant inhibitory forms of either CDC42 or Rac1 significantly inhibited antigen-induced degranulation. Altogether, our results demonstrate that CDC42 and Rac1 control distinct pathways downstream of FcepsilonRI engagement leading either to the induction of actin plaques, or to the production of membrane ruffles. These two pathways are critically involved during the degranulation response induced by Fc(epsilon)RI aggregation.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Joseph van de Wiel ◽  
Louise Meigh ◽  
Amol Bhandare ◽  
Jonathan Cook ◽  
Sarbjit Nijjar ◽  
...  

AbstractBreathing is highly sensitive to the PCO2 of arterial blood. Although CO2 is detected via the proxy of pH, CO2 acting directly via Cx26 may also contribute to the regulation of breathing. Here we exploit our knowledge of the structural motif of CO2-binding to Cx26 to devise a dominant negative subunit (Cx26DN) that removes the CO2-sensitivity from endogenously expressed wild type Cx26. Expression of Cx26DN in glial cells of a circumscribed region of the mouse medulla - the caudal parapyramidal area – reduced the adaptive change in tidal volume and minute ventilation by approximately 30% at 6% inspired CO2. As central chemosensors mediate about 70% of the total response to hypercapnia, CO2-sensing via Cx26 in the caudal parapyramidal area contributed about 45% of the centrally-mediated ventilatory response to CO2. Our data unequivocally link the direct sensing of CO2 to the chemosensory control of breathing and demonstrates that CO2-binding to Cx26 is a key transduction step in this fundamental process.


Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3271-3280 ◽  
Author(s):  
Istvan Szatmari ◽  
Daniel Töröcsik ◽  
Maura Agostini ◽  
Tibor Nagy ◽  
Mark Gurnell ◽  
...  

Abstract Activation of the lipid-regulated nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) modifies the immunophenotype of monocyte-derived dendritic cells (DCs). However it has not been analyzed in a systematic manner how lipid metabolism and immune regulation are connected at the transcriptional level via this receptor. Here we present the genome-wide expression analyses of PPARγ-instructed human DCs. Receptor activation was achieved by exogenous, synthetic as well as endogenous, natural means. More than 1000 transcripts are regulated during DC development by activation of PPARγ; half of the changes are positive effects. These changes appear to enhance and modulate the robust gene expression alterations associated with monocyte to DC transition. Strikingly, only genes related to lipid metabolism are overrepresented among early induced genes. As a net consequence, lipid accumulation appears to be diminished in these cells. In contrast, genes related to immune response are regulated after 24 hours, implying the existence of indirect mechanisms of modulation. Receptor dependence was established by using DCs of patients harboring a dominant-negative mutation of PPARγ. Our data show that PPARγ acts as a mostly positive transcriptional regulator in human developing DCs, acting primarily through controlling genes involved in lipid metabolism and via this, indirectly modifying the immune phenotype.


Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 599
Author(s):  
Michelle A. Kutzler

Spaying and neutering dogs is commonly used to prevent the birth of unwanted animals and eliminate the risk of reproductive diseases. However, removal of the gonads prevents the feedback of estrogen and testosterone on the pituitary and hypothalamus. As a result, luteinizing hormone (LH) is continuously elevated at supraphysiologic concentrations. Although the main role of LH is for reproductive function (e.g., ovulation), there are LH receptors present in several normal tissues including the thyroid and adrenal glands, gastrointestinal tract, cranial cruciate ligament and round ligament, and lymphocytes. In addition, there are LH receptors present in several neoplastic tissues (e.g., lymphoma, hemangiosarcoma, mastocytoma, transitional cell carcinoma, and osteosarcoma). The role of LH receptors in non-reproductive normal and neoplastic tissues is not known but may stimulate nitric oxide release and induce cell division. The precise etiology of the increased incidence of several non-reproductive long-term health complications following spaying and neutering is not known but may be related to LH receptor activation in these non-reproductive target tissues. How these effects may be mediated is described in this review.


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