Suppression Of Reproductive Function Research Articles

Inhibition of human androgen receptor by delta 9‐tetrahydro‐cannabinol and cannabidiol related to reproductive dysfunction: A computational study

There have been conflicting reports on the impact of Cannabis sativa impact on reproductive function. Hence this study was aimed to ascertain the impact of tetrahydrocannabinol (THC) and cannabidiol (CBD) binding affinity on human androgen receptor (AR) via computational molecular dynamic simulation. The human AR coordinate in this study is derived from human AR in complex with the ligand metribolone (R18) (PBD ID: 1E3G) template using (MODELER version. 9.15). CBD (PubChem CID: 644019), and THC (PubChem CID: 16078) 2D structures were retrieved from PubChem and docked (Autodock-Vina inbuilt in PyMol into the active site of human AR using the coordinates of the co-crystalized ligand (R18). All atomic representations in this study were created using visual molecular dynamics (VMD) tools. The result revealed that neither CBD nor THC bear significant 2D similarity with R18. Despite the diversity within the chemical space, both CBD and THC poses bond flexibility required to bind avidly to AR with the docking scores comparable to R18. In fully bound state, the three compounds engage the AR pocket hydrophobic residues such as L701, L704, and L707, and aromatic residues such as F764. Polar contacts with T877 observed in R18 bound state is avoided in the THC and CBD bound states. Moreso, the results revealed that CBD has lesser binding energy compared to THC and R18 compound which serves as standard. This study hypothesized that CBD and THC binds complimentarily to the pocket AR, indicating a likely inhibition of reproductive function and prostate cancer progression.

Suppression of reproductive function in juvenile rams by a slow-release gonadotropin-releasing hormone implant.

Background:Regarding animal welfare and reversible suppression of reproduction the need for alternatives to surgical castration, like slow-release gonadotropin-releasing hormone (GnRH) implants, is increasing.Aim:In this study, we evaluated whether the onset of puberty can be suppressed by implantation of a slow-release GnRH implant (4.7 mg deslorelin) in juvenile rams.Methods:Seven juvenile rams (3–5.5 months) were treated with the GnRH analog deslorelin to analyze the effects on testicular development, sonographic findings of testicular tissue, testosterone concentration in the blood, spermatogenesis, and sperm parameters from the epididymis after castration. Seven rams of the same age without an implant served as controls.Results:Follow-up examinations were conducted over 5 months, after which four rams per group were castrated. No significant group differences were found in the andrological parameters on the group level, but testicular development was suppressed in three rams in the treated group. Histological examination revealed spermatogenesis in the testicular tissue in three of four animals treated with a GnRH analog. Conclusion:The onset of puberty in juvenile rams cannot be reliably suppressed by using the slow-release GnRH implant Suprelorin®.

Central actions of insulin during pregnancy and lactation.

Pregnancy and lactation are highly metabolically demanding states. Maternal glucose is a key fuel source for the growth and development of the fetus, as well as for the production of milk during lactation. Hence, the maternal body undergoes major adaptations in the systems regulating glucose homeostasis to cope with the increased demand for glucose. As part of these changes, insulin levels are elevated during pregnancy and lower in lactation. The increased insulin secretion during pregnancy plays a vital role in the periphery; however, the potential effects of increased insulin action in the brain have not been widely investigated. In this review, we consider the impact of pregnancy on brain access and brain levels of insulin. Moreover, we explore the hypothesis that pregnancy is associated with site-specific central insulin resistance that is adaptive, allowing for the increases in peripheral insulin secretion without the consequences of increased central and peripheral insulin functions, such as to stimulate glucose uptake into maternal tissues or to inhibit food intake. Conversely, the loss of central insulin actions may impair other functions, such as insulin control of the autonomic nervous system. The potential role of low insulin in facilitating adaptive responses to lactation, such as hyperphagia and suppression of reproductive function, are also discussed. We end the review with a list of key research questions requiring resolution.

SAT-LB069 Differential Regulation of Hypothalamic and Hepatic Reproductive Signals by Leptin and Sex Steroids in the Mozambique Tilapia Oreochromis mossambicus

Reproduction is a physiologically demanding process that relies on energy sufficiency, the lack of which can result in delayed puberty and suppression of reproductive function. The pleiotropic peptide hormone leptin is a key signal in energy homeostasis that relays information on peripheral energy availability to central circuits. In mammals, leptin has been found to serve as a critical permissive signal in the activation of the gonadotropic axis and onset of puberty. Although leptin effects on reproduction have been explored extensively in mammals, its actions and regulatory properties on reproduction in fishes remain unclear. The current study assesses (i) the effect of in vivo leptin treatment on hypothalamic kisspeptin (kiss2) and gonadotropin-releasing hormone (gnrh1), (ii) the effect of leptin treatment on major egg-yolk precursors, vitellogenins (vtga, vtgb, vtgc), and insulin-like growth factor (igf1) in primary tilapia hepatocytes, and (iii) the effect of sex steroid treatment on leptin (lep) and insulin-like growth factor in primary tilapia hepatocytes. Gene expression of lep in the liver, the primary source of circulating hormone, increased with gonadosomatic index and sexual maturation of male and female tilapia, suggesting the hormone may regulate reproductive function. Intraperitoneal injection and 6-hour treatment with recombinant tilapia leptin (rtLep) in adult male tilapia resulted in increased hypothalamic kiss2 and gnrh1 transcript levels versus saline control (P < 0.01). In primary hepatocyte culture, rtLep suppressed vtgb and vtgc transcript levels (P < 0.01), while it stimulated igf1 (P < 0.0001). Testosterone and estradiol reduced lep levels (P < 0.001), but disparately regulated ­igf1 whereby testosterone increased igf1 and estradiol decreased igf1 at 10 and 100 nM (P < 0.001). The non-aromatizable 11-ketotestosterone increased lep and igf1 transcript levels at 100 nM (P < 0.05). Our findings suggest that leptin expression rises with sexual maturation and the hormone exerts stimulatory effects on hypothalamic gonadotropic factors. By contrast, leptin reduces estrogen-sensitive vitellogenesis while promoting elements of the somatotropic axis (e.g., igf1), suggesting the hormone may have dual roles in regulating reproductive and somatic growth processes. We speculate that this latter effect may be associated with limiting energy partitioning to reproduction in instances of negative energy balance. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

GnRH-agonist implantation of prepubertal male cats affects their reproductive performance and testicular LH receptor and FSH receptor expression

This study was conducted to investigate the effect of GnRH-agonist implantation in prepubertal tomcats on sexual behavior, reproductive performance, and expression of testicular LH receptor (LHR) and FSH receptor (FSHR) and also to compare the testicular characteristics, LHR and FSHR expression between prepubertal and adult tomcats. In experiment 1, 3-month-old tomcats (n = 6/group) were either treated with or left without 4.7 mg deslorelin implants. Semen collection and evaluation were performed just before castration at 48 weeks after treatment; removed testes were analyzed for mRNA and protein expression of LHR and FSHR. We were able to collect semen from six non-treated cats, whereas in treated cats, semen was uncollectable. The results revealed that sexual behavior was absent in the implanted cats throughout the study period. Testicular volume was found to decrease from 30 weeks after treatment onward in the implanted cats compared to the controls (P < 0.05). Semen production was found only in non-implanted cats. Testicular tissue score, seminiferous tubule diameter, and LHR protein expression were found lower in the implanted cats (P < 0.05), but no differences were observed in mRNA expression of LHR and protein expression of FSHR between groups. The mRNA expression of FSHR was higher in the implanted (P < 0.05) compared to control cats. In experiment 2, testes from prepubertal (n = 6) and adult (n = 6) male cats were collected after castration and analyzed for mRNA and protein expression of LHR and FSHR. No differences were observed in the protein expression of LHR and FSHR between the two groups, whereas mRNA expression of FSHR was higher in prepubertal cats (P < 0.05). Testicular and epididymal weight, diameter of seminiferous tubules, and the testicular grade were higher in the adult compared to prepubertal cats (P < 0.05). In conclusion, deslorelin implants suppressed protein expression of LHR and enhanced mRNA expression of FSHR along with suppression of reproductive function without any adverse effects for at least 48 weeks in male cats.

Putting the brakes on reproduction: Implications for conservation, global climate change and biomedicine

Seasonal breeding is widespread in vertebrates and involves sequential development of the gonads, onset of breeding activities (e.g. cycling in females) and then termination resulting in regression of the reproductive system. Whereas males generally show complete spermatogenesis prior to and after onset of breeding, females of many vertebrate species show only partial ovarian development and may delay onset of cycling (e.g. estrous), yolk deposition or germinal vesicle breakdown until conditions conducive for ovulation and onset of breeding are favorable. Regulation of this “brake” on the onset of breeding remains relatively unknown, but could have profound implications for conservation efforts and for “mismatches” of breeding in relation to global climate change. Using avian models it is proposed that a brain peptide, gonadotropin-inhibitory hormone (GnIH), may be the brake to prevent onset of breeding in females. Evidence to date suggests that although GnIH may be involved in the regulation of gonadal development and regression, it plays more regulatory roles in the process of final ovarian development leading to ovulation, transitions from sexual to parental behavior and suppression of reproductive function by environmental stress. Accumulating experimental evidence strongly suggests that GnIH inhibits actions of gonadotropin-releasing hormones on behavior (central effects), gonadotropin secretion (central and hypophysiotropic effects), and has direct actions in the gonad to inhibit steroidogenesis. Thus, actual onset of breeding activities leading to ovulation may involve environmental cues releasing an inhibition (brake) on the hypothalamo-pituitary–gonad axis.

Effectiveness of deslorelin acetate subcutaneous implantation in a domestic queen with after-spaying urinary incontinence

A 2-year-old female ovariectomised Norwegian Forest cat with a history of post-spaying urinary incontinence was diagnosed with acquired urinary sphincter mechanism incompetence (USMI) after complete clinical and laboratory examination. Although there is no literature regarding the treatment of post-spaying USMI in cats, deslorelin acetate is successful in the treatment of post-spaying USMI in dogs. Deslorelin acetate implants have been shown previously to be effective for contraception and oestrus suppression in queens, and suppression of reproductive function in tomcats. Therefore, deslorelin acetate implant treatment was chosen for treatment of post-spaying USMI in this queen. Follow-up examinations were performed on days 8, 15 and 30 after deslorelin implant insertion. Urinary continence was restored about 25 days after implantation and maintained for at least 15 months, without treatment-related negative effects. In the present case report, the post-spaying urinary incontinence related to the acquired USMI was successfully treated with a deslorelin acetate implant. In addition, safe implantation was easy in cats and the single injection resulted in long-lasting efficacy. Further studies are needed to confirm the usefulness of deslorelin acetate treatment for post-spaying USMI in queens and to better delineate the duration of efficacy.

Decreased luteinizing hormone pulse frequency is associated with elevated 24-hour ghrelin after calorie restriction and exercise in premenopausal women

Elevated ghrelin has been shown to be associated with reduced luteinizing hormone (LH) pulsatility in Rhesus monkeys, rats, men, and recently women. We previously reported that 24-h ghrelin concentrations are elevated in women following a 3-mo exercise and diet program leading to weight loss. We investigated whether the elevations in ghrelin following an ~3-mo exercise and diet program leading to weight loss are associated with a decrease in LH pulsatility. The nonexercising control group (Control, n = 5) consumed a controlled diet that matched energy needs, whereas energy intake in the exercise group (Energy Deficit, n = 16) was reduced from baseline energy requirements and supervised exercise training occurred five times per a week. Significant decreases in body weight (-3.0 ± 0.6 kg), body fat (-2.9 ± 0.4 kg) and 24-h LH pulse frequency (-0.18 ± 0.08 pulses/h), and a significant increase in 24-h mean ghrelin were observed in only the Energy Deficit group. The pre-post change in LH pulse frequency was negatively correlated with the change in mean 24-h ghrelin (R = -0.485, P = 0.030) and the change in peak ghrelin at lunch (R = -0.518, P = 0.019). Interestingly, pre-post change in night LH pulse frequency was negatively correlated with the change in mean day ghrelin (R = -0.704, P = 0.001). Elevated total ghrelin concentrations are associated with the suppression of LH pulsatility in premenopausal women and may play a role in the suppression of reproductive function following weight loss.

Physiological Research on Indices of Bull Sperm

Experimental data have found that the use of rations with high level of nitrates (0.43 g/kg body weight) led to significant increase in the level of serum lipid peroxidation in breeding bulls. Also there was observed inhibition of reproductive function in bulls and physiological indices of sperm.

Effects of kisspeptin on parameters of the HPA axis

The hypothalamo-pituitary-adrenal (HPA) and hypothalamo-pituitary-gonadal (HPG) axes have an intricate cross talk that results in the inhibition of reproductive functions during periods of chronic physiological or psychological stress. Recent studies have shown that kisspeptin neurons have projections to many non-reproductive areas of the brain including the paraventricular nucleus (PVN) of the hypothalamus, thereby providing evidence of an anatomical framework for kisspeptin to regulate the HPA axis. In this study, we tested as to whether kisspeptin modulates the HPA axis at three potential levels of regulation: (1) transcription of stress-related genes CRH, AVP, and oxytocin (OXY); (2) release of neuropeptides from PVN-derived neuronal cells via mobilization of intracellular calcium stores; and (3) in vivo regulation of the HPA axis under basal and stress-induced conditions in adult male rats. Overall, our data showed that kisspeptin did not alter basal, or stress-induced HPA axis activity (plasma corticosterone (CORT) and adrenocorticotropin hormone (ACTH)) in adult male rats and had modest, yet significant effects on CRH, AVP, and OXY gene expressions.

Beyond Leptin: Emerging Candidates for the Integration of Metabolic and Reproductive Function during Negative Energy Balance

Reproductive status is tightly coupled to metabolic state in females, and ovarian cycling in mammals is halted when energy output exceeds energy input, a metabolic condition known as negative energy balance. This inhibition of reproductive function during negative energy balance occurs due to suppression of gonadotropin-releasing hormone (GnRH) release in the hypothalamus. The GnRH secretagogue kisspeptin is also inhibited during negative energy balance, indicating that inhibition of reproductive neuroendocrine circuits may occur upstream of GnRH itself. Understanding the metabolic signals responsible for the inhibition of reproductive pathways has been a compelling research focus for many years. A predominant theory in the field is that the status of energy balance is conveyed to reproductive neuroendocrine circuits via the adipocyte hormone leptin. Leptin is stimulatory for GnRH release and lower levels of leptin during negative energy balance are believed to result in decreased stimulatory drive for GnRH cells. However, recent evidence found that restoring leptin to physiological levels did not restore GnRH function in three different models of negative energy balance. This suggests that although leptin may be an important permissive signal for reproductive function as indicated by many years of research, factors other than leptin must critically contribute to negative energy balance-induced reproductive inhibition. This review will focus on emerging candidates for the integration of metabolic status and reproductive function during negative energy balance.

Fertility control in a male rabbit using a deslorelin implant. A case report

Continuous low-dose release of the GnRH analogue deslorelin (Suprelorin, Peptech, Australia) causes a suppression of reproductive function in different species such as dogs, koalas, or kangaroos. No studies concerning the effi cacy and safety in male rabbits have yet been conducted. A male rabbit with hypospadia was introduced to the Clinic for Animal Reproduction. The owner intended to keep it together with a fertile female rabbit. To avoid reproduction, a 4.7 mg deslorelin implant was injected subcutaneously. No negative reaction to implant placement was diagnosed by daily examination of the injection site for one week. To test the effectiveness of the treatment, blood samples were taken and the testes size was measured regularly. After an initial rise in testosterone levels for 14 d, a down regulation for seven month with values lower than 0.1 ng/mL was observed. In the same period, the size of the testes declined to 50 % of the original dimensions. Afterwards, both testes regained their former shape and size. Since it was not a stud rabbit, semen parameters were not determined. During the suppression of the reproductive function, no sexual activity was observed by the owners. These fi ndings have yet to be proven by clinical trials with a suffi cient number of animals, but this case indicates the effi cacy of deslorelin implants in male rabbits.

Evaluation of the clinical efficacy of Gonazon implants in the treatment of reproductive pathologies, behavioral problems, and suppression of reproductive function in the male dog

Efficacy of a slow-release gonadotropin-releasing hormone (GnRH)-agonist implant (Gonazon) was assessed in 53 male dogs presented with benign prostatic hyperplasia (BPH), hypersexuality, aggressive behavior (either alone or in combination), excessive micturition, or to suppress fertility. Changes in testosterone (T) and estradiol (E2) concentrations and size of testes and prostate were monitored on Weeks 0, +8, and +26 after implantation. Additional measurements during and after this period were performed in 35 dogs. Clinical signs were assessed by the owners. All implants except one were retained throughout the study. Full downregulation of testicular function (T < 0.35 nmol/L) was achieved in 46 dogs, five dogs showed partial downregulation (T = 0.36 to 0.47 nmol/L), one dog did not respond, and another one displayed a transient downregulation on Week +18. On Week +8, mean T and E2 levels were reduced by 96% and 62%, respectively, and did not further decrease. Full downregulation (T < 0.35 nmol/L) lasted between 6 to >22 mo in most dogs except two. Compared with pretreatment values, mean testicular and prostatic size was reduced (P < 0.00001) by 54% and 52%, respectively, on Week +8 and by 68% and 64%, respectively, on Week +26. Relative reduction of prostatic size was more marked in dogs with BPH than in healthy ones on Week +8 (P < 0.05) and Week +26 (P < 0.02), and clinical signs of BPH disappeared rapidly after implantation. Dogs affected with BPH were significantly older (P < 0.001) than nonaffected ones (9.7 vs. 2.5 yr). Hypersexuality was more common in dogs < 3 yr of age, and treatment clearly improved clinical signs. Age significantly affected the response to treatment in aggressive dogs; 75% of the cases responded with an improvement. The only minor and possibly treatment-related events observed were a short-lasting exacerbation of clinical signs of BPH (two dogs), increased weight gain (three dogs), and anxiety (three dogs) with one of these dogs developing a blunt coat. These results demonstrate the clinical efficacy and overall safety of the Gonazon implants.

Sexual behavior in lactating rats: Role of estrogen-induced progesterone receptors

Lactation is associated with suppression of reproductive function, the duration of which depends on the number of young suckled and food availability. Although previous studies have documented increasing responsivity to the positive feedback effects of estrogen on luteinizing hormone (LH) secretion with time postpartum, changes in the ability of estrogen to stimulate sexual behavior across these time points and the influence of food restriction on response to estrogen have not been investigated. Thus, we compared the ability of exogenous estrogen administration to stimulate proceptive and receptive behavior in ad libitum fed and food restricted rats on Days 15 and 20 postpartum. Because the ability of estrogen to induce sexual behavior depends on activation of both estrogen receptors and estrogen-induced progesterone receptors, a second study compared estrogen and progesterone-ir within the VMH and MPOA in similar groups. Finally, we investigated the role of the high levels of progesterone typical of lactation in the suppression of estrogen-induced sexual behavior by transient blockade of the progesterone receptor using RU486. As expected there was an increase across time in the ability of estrogen to stimulate sexual behavior that correlated with an increased ability of estrogen to induce progesterone receptors in the MPOA that was most evident in ad libitum fed rats. RU486 administration concomitant with estrogen administration increased solicitation behavior and was most effective in ad libitum fed rats suggesting an inhibitory role of progesterone on estrogen-induced sexual proceptivity in lactating rats.

RESPONSE

Dear Editor-in-Chief: The writing group for the ACSM Position Stand on the female athlete triad thanks Dr. Lamont for her letter concerning the dietary protein needs of the female athlete. We do think that suppression of reproductive function and bone protein synthesis in severely undernourished female athletes may reflect a protein deficiency as well as an energy deficiency, but we agree that scientifically credible methods for measuring protein requirements for health and performance are lacking. We also agree that correcting an energy deficiency with a mixed diet will probably correct whatever currently unknowable protein deficiency there may also be. Because of many of the issues raised by Dr. Lamont, we had not planned on including the protein recommendation in the document, but we were requested to do so in the final review process. Aurelia Nattiv, MD, FACSM David Geffen School of Medicine University of California, Los Angeles Los Angeles, CA Melinda M. Manore, PhD, RD, FACSM College of Health and Human Sciences Oregon State University Corvallis, OR

CrossRef Listing of Deleted DOIs

The etiology of amenorrhea in exercising women is linked to a mismatch between caloric intake and high levels of exercise energy expenditure that results in a chronic energy deficit. This in turn stimulates compensatory mechanisms such as weight loss, metabolic hormone alterations, or energy conservation that subsequently causes a central suppression of reproductive function and concomitant hypoestrogenism. This suppression of reproductive function is associated with stress fractures, loss of bone mineral density, the failure to achieve peak bone mass, osteopenia, and osteoporosis. It has generally been accepted that the chronic hypoestrogenism is the major cause of bone loss in exercising women. However, the effects of food restriction and energy deficiency on bone mineral density likely represents an estrogen-independent mechanism for bone loss that involves some of the metabolic-related hormones altered with exercise-associated amenorrhea. These hormones (IGF-1 and leptin) play an important role in modulating bone turnover and bone mineral density in these women.

Astressin B, a Nonselective Corticotropin-Releasing Hormone Receptor Antagonist, Prevents the Inhibitory Effect of Ghrelin on Luteinizing Hormone Pulse Frequency in the Ovariectomized Rhesus Monkey

Administration of ghrelin, a key peptide in the regulation of energy homeostasis, has been shown to decrease LH pulse frequency while concomitantly elevating cortisol levels. Because increased endogenous CRH release in stress is associated with an inhibition of reproductive function, we have tested here whether the pulsatile LH decrease after ghrelin may reflect an activated hypothalamic-pituitary-adrenal axis and be prevented by a CRH antagonist. After a 3-h baseline LH pulse frequency monitoring, five adult ovariectomized rhesus monkeys received a 5-h saline (protocol 1) or ghrelin (100-microg bolus followed by 100 microg/h, protocol 2) infusion. In protocols 3 and 4, animals were given astressin B, a nonspecific CRH receptor antagonist (0.45 mg/kg im) 90 min before ghrelin or saline infusion. Blood samples were taken every 15 min for LH measurements, whereas cortisol and GH were measured every 45 min. Mean LH pulse frequency during the 5-h ghrelin infusion was significantly lower than in all other treatments (P < 0.05) and when compared with the baseline period (P < 0.05). Pretreatment with astressin B prevented the decrease. Ghrelin stimulated cortisol and GH secretion, whereas astressin B pretreatment prevented the cortisol, but not the GH, release. Our data indicate that CRH release mediates the inhibitory effect of ghrelin on LH pulse frequency and suggest that the inhibitory impact of an insufficient energy balance on reproductive function may in part be mediated by the hypothalamic-pituitary-adrenal axis.

Corticotropin-Releasing Hormone and Pro-Opiomelanocortin Gene Expression in Female Monkeys with Differences in Sensitivity to Stress

Background/Aims: The expressions of corticotropin-releasing hormone (CRH) and pro-opiomelanocortin (POMC) were assessed in brain tissue collected from nonstressed female cynomolgus monkeys previously categorized as highly stress resilient (HSR), medium stress resilient (MSR), or stress sensitive (SS) with respect to stress-induced anovulation. Methods: In situ hybridization and quantitative image analysis was used to measure mRNAs coding for CRH in the hypothalamic paraventricular nucleus (PVN) and thalamic center median-subfascicular complex (CM-Sf). Then, CRH neurons in the PVN were immunostained and the area of immunostaining was measured. Also, CRH fibers were immunostained in the central nucleus of the amygdala and the area of immunostaining was obtained. Finally, POMC mRNA expression was characterized in the hypothalamic infundibular nucleus. The groups were compared with ANOVA and Student-Newman-Keul’s (SNK) post hoc comparison. Results: CRH mRNA was significantly elevated in the caudal PVN in the MSR and SS animals compared to HSR animals (p < 0.05, SNK). There was a significant increase in average and total CRH-positive area in the MSR and SS groups compared to the HSR group (p < 0.05, SNK). There was also a significant increase in CRH volume in the MSR and SS groups compared to the HSR group (p < 0.05, SNK). In the CM-Sf, the average CRH optical density was significantly higher in the MSR and SS groups than in the HSR group (p < 0.05, SNK). In the central nucleus of the amygdala, the area of CRH fiber staining was significantly higher in the SS group than in the MSR or HSR groups (p < 0.05, SNK). There was no difference between the groups in POMC mRNA expression in the mediobasal hypothalamus. Conclusion: Macaques that exhibit immediate suppression of reproductive function upon stress are considered stress sensitive. These animals have elevated CRH in the hypothalamus and limbic structures, which may play a role in suppressing the hypothalamic-gonadal axis upon stress initiation.

Taking it a step too far? Physical activity and infertility

Purpose – Public health messages are a constant reminder, informing us that we need to participate in more physical activity. Such messages when coupled with increased social pressures can mean that vulnerable women are at risk of over‐exercising. Research indicates that light‐to‐moderate physical activities are associated with most favourable health outcomes. Intense activities, however, may actually have detrimental effects, including suppression of reproductive function. The aim of this paper is to give a balanced overview discussing how physical activity can affect female health, with a particular focus on fertility.Design/methodology/approach – The most up‐to‐date and pertinent studies within the literature have been included and summated in this review.Findings – Statistics indicate that approimately half‐a‐million (443,116) women in the UK are infertile. Furthermore, many women experience some degree of subfertility, although a prevalence rate has not yet been established. Research indicates that r...

Immunological influences on reproductive neuroendocrinology

One of the consequences of activation of the immune system, with its associated inflammatory responses and operation of the stress axes, is a generalised inhibition of reproductive function. This can be considered as part of the all-encompassing effects of an activated immune system, included in which is the 'immunological cost' arising from the nutritional demand required to maintain a competent, responsive immune system, and the pathological effects produced by severe immune responses. Elucidation of specific immune-neuroendocrine linkages has largely involved examination of corticosteroid-based mechanisms or use of bacterial endotoxin as a model stimulus and examination of effects on GnRH and LH pulsatility, on GnRH and LH surge processes and on pituitary responsiveness to GnRH, using various sheep models. Although there is good evidence for prostaglandins as common mediators for endotoxin-induced and stress axis-induced impairment of neuroendocrine reproductive processes, both mechanisms appear to have prostaglandin-independent pathways as well. At the anterior pituitary gland level, the type II glucocorticoid receptor appears to mediate corticosteroid effects. Otherwise, the identity of specific cytokines, their sites of action and the cell level mechanisms underlying the inhibition of the reproductive axis at hypothalamic and anterior pituitary levels, especially in sheep, remains largely unresolved.