Estradiol Implants Research Articles

Adolescent development of anxiety-related behavior and shifts in behavioral responsiveness to estradiol in female mice.

Early pubertal onset during adolescence is consistently linked with increased risk of anxiety and depression in girls. Although estradiol tends to have anxiolytic effects in adulthood, whether sensitivity to estradiol's anxiolytic actions increases during adolescence is not clear. Using a rodent model, the current study tested the hypothesis that a shift in sensitivity to the anxiolytic effects of estradiol occurs during adolescence. To test this hypothesis, prepubertal and adult C57BL/6 female mice were ovariectomized, implanted with vehicle- or estradiol-filled silastic capsules, and behavioral tested one week later in the open field and elevated zero maze. Our hypothesis predicted that estradiol would decrease anxiety-related behavior to a greater extent in adults than in adolescent females, however, our results did not support this hypothesis. In the open field, estradiol implants significantly decreased anxiety-like behavior in adolescent females (relative to vehicle) and had little to no effect on the behavior of adults. These data suggest that adolescence is associated with a downward shift in sensitivity to the anxiolytic effects of estradiol on behavior in the open field. In contrast, although estradiol treatment did not influence anxiety-like responses in the elevated zero maze in early adolescent or adult females, adolescent females displayed significantly higher levels of anxiety-like behavior than adults. These findings demonstrate that substantial changes in anxiety-related behavior occur during adolescence, including a context-dependent shift in behavioral responsiveness to estradiol.

Corrigendum to: Oestradiol implants for gender-affirming hormone therapy: an observational study of serum oestradiol levels and consumer survey.

Corrigendum to: Oestradiol implants for gender-affirming hormone therapy: an observational study of serum oestradiol levels and consumer survey.

Effects of gender affirming hormone treatment in transgender individuals - a retrospective cohort study.

Gender affirming hormone treatment (GAHT) results in measurable changes to anthropomorphic, biochemical and hormonal variables that are important to patients and their health care professionals to guide treatment. This study sought to quantify changes which occur in response to initiation of GAHT. We performed a retrospective cohort study of outcomes in transgender and gender diverse (TGD) patients starting GAHT. The primary outcome was proportion of patients and time required to achieve optimal hormone levels after commencement of GAHT. Additional analyses were performed to assess whether clinical and biochemical factors were associated with likelihood of achieving target hormone levels. 345 patients were included. Among 154 transmasculine individuals, 116 (75%) achieved a testosterone level >10 nmol/L during follow-up at a median of 4-months (IQR 4-9). No clinical or biochemical factors were significantly associated with likelihood of reaching therapeutic testosterone concentrations in transmen. Among 191 transfeminine individuals, 131 (72%) achieved a testosterone level <2.0 nmol/L during follow-up at a median of 4-months (IQR 3-9). Factors associated with increased likelihood of testosterone suppression were use of subdermal estradiol implants as well as cyproterone acetate as an androgen antagonist. Changes in differing directions were observed during repeated measures of lipids, liver function, and blood count between transmasculine and transfeminine individuals, reflecting the important effects of testosterone and estradiol on biochemical tests ordered as part of routine clinical care. Most TGD patients achieve target testosterone levels within 9 months of GAHT initiation. Adverse effects of GAHT are rare, and are usually mild.

Induction of precocious females in the protandrous barramundi (Lates calcarifer) with long-acting estradiol implants

Induction of precocious females in the protandrous barramundi (Lates calcarifer) with long-acting estradiol implants

157 Daily Versus Three Times a Week Ddgs Supplementation on Grazing Calves

Abstract Supplemental feed may be provided to cattle in grazing systems to increase ADG, but can be labor intensive. This study evaluated the performance of steers grazing smooth bromegrass pastures supplemented dried distillers grains plus solubles (DDGS) either daily or three times per week. Crossbred steers (n = 144, initial BW 317 ± 1.25 kg) were used in a randomized complete block design with 3 treatments allocated randomly to 24 paddocks in one of 6 blocks. Treatments consisted of: 1) steers supplemented daily with 0.8% of BW (DM-basis) of DDGS, 2) steers supplemented three times a week with 1.86% of BW (DM-basis) of DDGS, and 3) steers that received no supplementation (control). All steers were implanted with 40 mg trenbolone acetate and 8 mg estradiol (Rev-G; Merck Animal Health, De Soto, KS) implants. Paddocks were divided equally into three strips and rotationally grazed. Put-and-take steers were utilized to match stocking rate with forage growth. Each treatment group rotated through three 0.81-hectare strips per pasture. Pre-graze and post-graze biomass was measured at ground level from each paddock at each rotation. Pre-graze biomass samples were used to determine forage availability. Grazing was initiated in early May with cattle removed from pastures in August, for a total of 97 grazing days. Data were analyzed with MIXED procedure of SAS with paddock as experimental unit and treatment and block as fixed effects. Treatment means of ADG and ending BW differed (P &amp;lt; 0.01) among treatments. The control calves gained 0.85 kg/d. The supplemented treatments significantly increased (P &amp;lt; 0.01) ADG compared with the control, with daily supplementation gaining 1.25 kg/d and 3x gaining 1.11 kg/d. The ADG was decreased (P &amp;lt; 0.01) with 3x a week compared with daily supplementation. The differences in ADG resulted in similar differences in final live BW. The control had a finial live BW of 398 kg and final live BW of both supplemented treatments was significantly increased (P &amp;lt; 0.01) when compared with the control treatment. Final live BW of 3x supplemented steers (423 kg) was decreased (P &amp;lt; 0.01) when compared with daily supplemented steers (436 kg). For steers grazing smooth bromegrass pastures, daily supplementation of DDGS resulted in greater gains and therefore greater final BW when compared with three times a week supplementation and the non-supplemented control.

Induced Sex Reversal in Adult Males of the Protandric Hermaphrodite Centropomus undecimalis Using 17 β-Estradiol: Enhancing Management Strategies for Captive Broodstock

The common snook (Centropomus undecimalis) is a protandric hermaphrodite fish that undergoes a sex change during its life cycle. In nature, common snook females develop directly from males shortly after spawning. However, the factors triggering this process remain unknown. This knowledge gap poses challenges for managing the species in captivity. To address this, we conducted a study on sex change induction in three-year-old males using estradiol and evaluated the potential effects of photoperiod manipulation on early maturation. Four treatment groups were employed: (1) fish with estradiol + natural photoperiod; (2) fish without estradiol + natural photoperiod; (3) fish without estradiol + controlled photoperiod; and (4) fish with estradiol + controlled photoperiod. The effectiveness of these treatments was assessed through histological procedures, which allowed for the examination of the fishes’ gonads. Furthermore, the concentration of alkali labile phosphorus in fish plasma was measured and correlated with the histological results. Our findings revealed that administering 2 mg/kg estradiol implants resulted in a remarkable 100% female population within the estradiol-treated groups. No significant effect on fish maturation was observed due to the manipulated photoperiod conditions. This protocol offers improved management strategies for captive broodstock. Firstly, the concentration of estradiol used in this study proved sufficient to induce sex change in this hermaphroditic species, enabling the production of viable females at an early age and smaller size and facilitating easier broodstock manipulation. Secondly, the implementation of the alkali labile phosphorus technique allows for sex identification without the need to sacrifice the fish. In conclusion, our study provides valuable insights into sex change induction and photoperiod manipulation in common snook. The findings contribute to enhanced management practices for captive broodstock. However, further research is needed to explore the underlying mechanisms triggering sex change and to optimize protocols for long-term maintenance and successful reproduction in captivity.

Effect of estradiol and predator cues on behavior and brain responses of captive female house sparrows (Passer domesticus).

The presence of predators can cause major changes in animal behavior, but how this interacts with hormonal state and brain activity is poorly understood. We gave female house sparrows (Passer domesticus) in post-molt condition an estradiol (n = 17) or empty implant (n = 16) for 1week. Four weeks after implant removal, a time when female sparrows show large differences in neuronal activity to conspecific vs. heterospecific song, we exposed birds to either 30min of conspecific song or predator calls, and video recorded their behavior. Females were then euthanized, and we examined neuronal activity using the expression of the immediate early gene (IEG) ZENK to identify how the acoustic stimuli affected neuronal activation. We predicted that if female sparrows with estradiol implants reduce neuronal activity in response to predator calls as they do to neutral tones and non-predatory heterospecifics, they would show less fear behavior and a decreased ZENK response in brain regions involved in auditory (e.g., caudomedial mesopallium) and threat perception functions (e.g., medial ventral arcopallium) compared to controls. Conversely, we predicted that if females maintain auditory and/or brain sensitivity towards predator calls, then female sparrows exposed to estradiol would not show any differences in ZENK response regardless of playback type. We found that female sparrows were less active during predator playbacks independent of hormone treatment and spent more time feeding during conspecific playback if they had previously been exposed to estradiol. We observed no effect of hormone or sound treatment on ZENK response in any region of interest. Our results suggest that female songbirds maintain vigilance towards predators even when in breeding condition.

Steroid hormone imbalance drives macrophage infiltration and Spp1/osteopontin+ foam cell differentiation in the prostate.

Benign prostatic hyperplasia (BPH) occurs progressively with aging in men and drives deteriorating symptoms collectively known as lower urinary tract symptoms (LUTS). Age-associated changes in circulating steroid hormones, and prostate inflammation have been postulated in the etiology of BPH/LUTS. The link between hormones and inflammation in the development of BPH/LUTS is conflicting because they may occur independently or as sequential steps in disease pathogenesis. This study aimed to decipher the prostatic immune landscape in a mouse model of lower urinary tract dysfunction (LUTD). Steroid hormone imbalance was generated by the surgical implantation of testosterone (T) and estradiol (E2) pellets into male C57BL/6J mice and gene expression analysis was performed on ventral prostates (VPs). These experiments identified an increase in the expression of macrophage markers and Spp1/osteopontin (OPN). Localization studies of OPN pinpointed that OPN+ macrophages travel to the prostate lumen and transition into lipid-accumulating foam cells. We also observed a significant increase in the number of tissue macrophages in the VP which was prevented in OPN-knockout (OPN-KO) mice. In contrast, mast cells, but not macrophages, were significantly elevated in the dorsal prostate of T + E2-treated mice which was diminished in OPN-KO mice. Steroid hormone implantation progressively increased urinary frequency, which was ameliorated in OPN-KO mice. Our study underscores the role of age-associated steroid hormone imbalances as a mechanism of expanding the prostatic macrophage population, their luminal translocation, and foam cell differentiation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Effect of hormonal therapy on the otoconial changes caused by estrogen deficiency

Benign paroxysmal positional vertigo (BPPV) is associated with menopause and/or osteopenia. Morphological changes in the otoconial layer have been reported after ovariectomy (OVX). Moreover, hormone replacement therapy decreases BPPV risk. However, knowledge concerning the effect of hormonal therapy on the otoconial changes caused by estrogen deficiency is limited. We aimed to examine the effect of hormonal therapy on otoconial changes caused by estrogen deficiency. We hypothesized that hormonal therapy could reduce otoconial changes caused by OVX. Eight-week-old C57BL/6 mice were divided into four groups: sham operation with implantation of vehicle (sham + v), OVX with implantation of vehicle (OVX + v), OVX with implantation of estradiol (E2) (OVX + E2), and OVX with implantation of raloxifene (RAL) (OVX + RAL) groups. Otoconial layer volume was measured by micro-CT at 4 weeks after OVX or the sham operation. The otic bullae were removed; immunohistochemistry was performed for estrogen receptor alpha and 4-hydroxynonenal. Otoconial layer volume was significantly higher in the OVX + v than in the sham + v group. E2 and RAL significantly reduced these changes in the endometrial layer. The staining of estrogen receptor alpha and 4-hydroxynonenal were stronger in the OVX + v than in the sham + v group but equal in the sham + v, OVX + E2, and OVX + RAL groups. These results indicate that E2 and RAL are effective against morphological changes of the otoconial layer caused by estrogen deficiency via oxidative stress reduction.

A collaborative model aligning adult sexual health and endocrine gender health services.

The Hunter New England (HNE) endocrinology and sexual health service commenced a co-located gender community clinic in 2018. This paper describes this novel model of service delivery, including the sociodemographics, clinical characteristics, and STI screening rates of trans and gender diverse (TGD) adults attending for gender-affirming hormone treatment (GAHT) and identifies patients accessing the broader skill set of both specialty services in 2018-19. This study was a retrospective audit of medical records of all patients with initial consultations for GAHT at the endocrine and sexual health gender clinics from 1 January 2018 to 31 December 2019. A further data set included any adult TGD patient with any attendance, initial or subsequent, between 1 January 2018 and 31 December 2019. Patients with dual attendance at the endocrine gender clinic and sexual health service were further explored. Baseline sociodemographic data of participants were comparable in both gender clinics attended. Endocrinologists were more likely to use spironolactone for androgen blockade than the sexual health physician (77.8% vs 43.8%, P =0.0096), but prescribing patterns were otherwise similar. STI screening was more frequently performed in patients accessing GAHT through sexual health than endocrine gender clinics (35% vs 0.9%, P =0.00). Twenty patients (8.0%) had an attendance at both the sexual health and endocrine services and accessed STI screening, contraception, cervical screening, HIV pre- or post-exposure prophylaxis and estradiol implants. Co-located gender clinics staffed by endocrinology and sexual health physicians provide care for a similar patient population and facilitate access to GAHT, estradiol implants, STI screening, contraception, and cervical screening for the TGD population.

Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice.

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

Effect of trenbolone acetate, melengestrol acetate, and ractopamine hydrochloride on the growth performance of beef cattle

The effect of trenbolone acetate + estradiol (TBA) implants, melengestrol acetate (MGA), and ractopamine hydrochloride + TBA (RAC + TBA) on growth performance and carcass characteristics in beef cattle (n = 680; 279 ± 10.1 kg) fed barley grain/corn silage was examined in a 4 yr study (four pens per treatment per year; 262 ± 8 d feeding period). In the first 2 yr, treatments were (1) control heifers (H-CON; no growth promoters), (2) TBA-implanted heifers (H-TBA), (3) MGA heifers (H-MGA), (4) control steers (S-CON; no growth promoters), and (5) TBA-implanted steers (S-TBA). A sixth treatment (6) RAC + TBA steers (RAC + TBA) was included in years 3 and 4. Overall dry matter intake (DMI) of heifers was increased (P &lt; 0.001) by TBA but not MGA. Compared with H-CONs, H-TBA had greater average daily gain (ADG) (P &lt; 0.001), gain to feed ratio (G/F) (P &lt; 0.001), and carcass weight (P &lt; 0.001), whereas S-TBA had increased ADG (P &lt; 0.001), G/F (P&lt; 0.001), and carcass weight (P &lt; 0.001) compared with S-CON. Compared with H-CON, H-MGA had increased (P &lt; 0.01) ADG, G/F, and carcass weight. The RAC + TBA had increased (P &lt; 0.01) ADG and carcass weight (3.2%) but not G/F or DMI compared with S-TBA. This 4 yr study showed a consistent positive impact of growth-enhancing technologies on the performance of Canadian feedlot cattle.

Low complication rates of testosterone and estradiol implants for androgen and estrogen replacement therapy in over 1 million procedures.

Background:Testosterone (T) deficiency (TD) in men and women and estrogen (E) deficiency (ED) in women increasingly affects the overall health and quality of life of patients. T implants have seen increased utilization over the past decade. We evaluated continuation rates and adverse events that occurred during T therapy by reviewing practitioner reported data on compressed human-identical T implants for the treatment of TD in both men and women collected over 7 years.Methods:This was a retrospective review of data collected prospectively from men and women from 2012 and 2019. Men who had the clinical syndrome of TD received subcutaneous T implant therapy. Women who presented with symptoms of TD and/or ED underwent T implant and/or estradiol implant therapy. The clinics spanned multiple specialties including obstetrics and gynecology, internal medicine, family practice, and urology. Data were entered into a secure, custom tracking App, using Azure App Services and MS SQL Database integrated with a proprietary dosing site and industry-leading Pharmacy Dispensing software (BioTracker®).Results:Over the 7 years, 1,204,012 subcutaneous implant procedures were performed for 376,254 patients; 85% of the procedures were performed in women. Of the women, 54% of were premenopausal, and 46% were postmenopausal. The overall continuation rate after two insertions was 93%. The overall complication rate was <1%. Most common secondary response reported was pellet extrusion, which was more common in men (<3%) than women (<1%).Conclusions:This study is the largest reported retrospective study to evaluate the continuation and complication rates of T pellet implants. The safety of subcutaneous hormone pellet implants in men and women appears to be better than other routes of administration of bioidentical hormone replacement therapy. Further investigations on short- and long-term benefits of this modality are ongoing and could expand the overall utilization of this method.

164 Effect of trenbolone acetate, melengestrol acetate, and ractopamine hydrochloride on growth performance of growing beef cattle

Abstract This study evaluated the effect of trenbolone acetate + estradiol implants (TBA), melengestrol acetate (MGA), and ractopamine hydrochloride (RAC) on the performance of beef cattle fed barley grain/corn silage diets. Beef cattle (279 ± 10.1 kg) were used in a complete randomized 4-yr study (yr 1, 2, n = 120 heifers and 80 steers; yr 3, 4, n = 120 heifers and 120 steers). Cattle were blocked by weight and randomly assigned to 4 pens/treatment/yr. Treatments were 1) control heifers [no growth promoters (GP)], 2) TBA implanted heifers, 3) MGA heifers, 4) control steers (no GP), and 5) TBA implanted steers (yrs 1 to 4), and included a sixth treatment 6) TBA implanted + RAC steers for yrs 3 and 4. Cattle were fed for a similar duration (262 d ± 8) in all treatments. TBA increased the DMI of steers and heifers (P &amp;lt; 0.001) compared to controls (9.52 vs. 8.73 kg DM/d). MGA did not affect DMI (P = 0.41); however, TBA+RAC steers had grater DMI (P = 0.02; 9.91 vs. 9.58 kg DM/d) compared to TBA steers. Compared to controls, TBA heifers had greater ADG (P &amp;lt; 0.001; 1.45 vs. 1.29 kg), G:F (P &amp;lt; 0.001; 0.157 vs. 0.149), and carcass weight (P &amp;lt; 0.001; 390 vs. 360 kg). TBA also increased steers ADG (P &amp;lt; 0.001; 1.70 vs. 1.41 kg), G:F (P &amp;lt; 0.001; 0.174 vs. 0.161), and carcass weight (P &amp;lt; 0.001; 425 vs. 389 kg). Compared to control heifers, MGA increased (P &amp;lt; 0.01) ADG, G:F, and carcass weight by 8.1%, 7.0%, and 4.7%, respectively. The ADG and carcass weight of TBA+RAC steers increased (P &amp;lt; 0.01) by 5.6% and 3.2%, respectively with no effect (P = 0.87) on G:F compared to TBA steers. This 4-yr study demonstrates the consistent positive impact of conventional growth-enhancing technologies.

Morphological and functional evidence for sexual dimorphism in neurokinin B signalling in the retrochiasmatic area of sheep.

Neurokinin B (NKB) is critical for fertility in humans and stimulates gonadotrophin-releasing hormone/luteinising hormone (LH) secretion in several species, including sheep. There is increasing evidence that the actions of NKB in the retrochiasmatic area (RCh) contribute to the induction of the preovulatory LH surge in sheep. In the present study, we determined whether there are sex differences in the response to RCh administration of senktide, an agonist to the NKB receptor (neurokinin receptor-3 [NK3R]), and in NKB and NK3R expression in the RCh of sheep. To normalise endogenous hormone concentrations, animals were gonadectomised and given implants to mimic the pattern of ovarian steroids seen in the oestrous cycle. In females, senktide microimplants in the RCh produced an increase in LH concentrations that lasted for at least 8hours after the start of treatment, whereas a much shorter increment (approximately 2hours) was seen in males. We next collected tissue from gonadectomised lambs 18hours after the insertion of oestradiol implants that produce an LH surge in female, but not male, sheep for immunohistochemical analysis of NKB and NK3R expression. As expected, there were more NKB-containing neurones in the arcuate nucleus of females than males. Interestingly, there was a similar sexual dimorphism in NK3R-containing neurones in the RCh, NKB-containing close contacts onto these RCh NK3R neurones, and overall NKB-positive fibres in this region. These data demonstrate that there are both functional and morphological sex differences in NKB-NK3R signalling in the RCh and raise the possibility that this dimorphism contributes to the sex-dependent ability of oestradiol to induce an LH surge in female sheep.

GPER1 Signaling Initiates Migration of Female V-SVZ-Derived Cells.

SummaryIn the rodent ventricular-subventricular zone (V-SVZ) neurons are generated throughout life. They migrate along the rostral migratory stream (RMS) into the olfactory bulb before their final differentiation into interneurons and integration into local circuits. Estrogen receptors (ERs) are steroid hormone receptors with important functions in neurogenesis and synaptic plasticity. In this study, we show that the ER GPER1 is expressed in subsets of cells within the V-SVZ of female animals and provide evidence for a potential local estrogen source from aromatase-positive astrocytes surrounding the RMS. Blocking of GPER1 in Matrigel cultures of female animals significantly impairs migration of V-SVZ-derived cells. This outgrowth is accompanied by regulation of phosphorylation of the actin-binding protein cofilin by GPER1 signaling including an involvement of the p21-Ras pathway. Our results point to a prominent role of GPER1 in the initiation of neuronal migration from the V-SVZ to the olfactory bulb.

The effects of zeranol and oestradiol implants on performance and nutrient digestibility of zero-grazed White Fulani cattle

Aim The aim of this study was to investigate the effects of two growth-promoting implants (zeranol and oestradiol-17β) on performance and feed digestibility of finishing White Fulani cattle in the feedlot. This was with a view to determining an alternative means of enhancing cattle performance without grazing the animals. Methods A 60-day feedlot trial was conducted using 27 stocker White Fulani bulls that were allotted randomly to three treatment groups (i.e. non-implanted, oestradiol-implanted and zeranol-implanted) in a completely randomised experimental design. Cattle were offered a compounded feedlot ration consisting of 14% crude protein ad libitum. The bulls were weighed initially and fortnightly thereafter for the duration of the study. Coefficients of dry matter and nutrients digestibility were determined using lignin as an internal marker. Data were analysed using the general linear model procedure of ANOVA and mean values were compared using Fisher’s least significant difference (l.s.d.0.05). Key results The average final liveweight, total weight gain, average daily gain (ADG) and average daily feed intake (ADFI) of implanted feedlot cattle were higher (P &amp;lt; 0.05) than for non-implanted cattle; and higher in oestradiol-implanted cattle compared with zeranol-implanted ones. The ADG was 29.16 and 20.48% higher, and the ADFI was 35.06 and 18.18% higher for oestradiol-implanted and zeranol-implanted feedlot cattle, respectively than for non-implanted cattle. Irrespective of the treatment, feed conversion ratio of experimental bulls remained below the range (4.5–7.5) established for feedlot beef cattle; an indication of better efficiency of feed utilisation by White Fulani cattle. The apparent digestibility of dry matter (59.76–64.31%) of the feedlot ration was in the order: non-implanted = oestradiol-implanted &amp;gt; zeranol-implanted while the apparent digestibility of crude protein (73.91–77.99%) was in the order: non-implanted &amp;gt; oestradiol-implanted = zeranol-implanted. Conclusions and implications The results of this study show that the use of an oestradiol implant in finishing zero-grazed White Fulani cattle was beneficial for improving growth performance. Both implanted and non-implanted cattle showed good coefficients of nutrient digestibility, indicating that the mode of action of the growth implants in enhancing performance characteristics does not depend on indices of digestibility.

Effects of exposure to 12C and 4He particles on cognitive performance of intact and ovariectomized female rats

Exposure to the types of radiation encountered outside the magnetic field of the earth can disrupt cognitive performance. Exploratory class missions to other planets will include both male and female astronauts. Because estrogen can function as a neuroprotectant, it is possible that female astronauts may be less affected by exposure to space radiation than male astronauts. To evaluate the effectiveness of estrogen to protect against the disruption of cognitive performance by exposure to space radiation intact and ovariectomized female rats with estradiol or vehicle implants were tested on novel object performance and operant responding on an ascending fixed-ratio reinforcement schedule following exposure to 12C (290 MeV/n) or 4He (300 MeV/n) particles. The results indicated that exposure to carbon or helium particles did not disrupt cognitive performance in the intact rats. Estradiol implants in the ovariectomized subjects exacerbated the disruptive effects of space radiation on operant performance. Although estrogen does not appear to function as a neuroprotectant following exposure to space radiation, the present data suggest that intact females may be less responsive to the deleterious effects of exposure to space radiation on cognitive performance, possibly due to the effects of estrogen on cognitive performance.

Changes in Both Neuron Intrinsic Properties and Neurotransmission Are Needed to Drive the Increase in GnRH Neuron Firing Rate during Estradiol-Positive Feedback.

Central output of gonadotropin-releasing hormone (GnRH) neurons controls fertility and is sculpted by sex-steroid feedback. A switch of estradiol action from negative to positive feedback initiates a surge of GnRH release, culminating in ovulation. In ovariectomized mice bearing constant-release estradiol implants (OVX+E), GnRH neuron firing is suppressed in the morning (AM) by negative feedback and activated in the afternoon (PM) by positive feedback; no time-of-day-dependent changes occur in OVX mice. In this daily surge model, GnRH neuron intrinsic properties are shifted to favor increased firing during positive feedback. It is unclear whether this shift and the observed concomitant increase in GABAergic transmission, which typically excites GnRH neurons, are independently sufficient for increasing GnRH neuron firing rate during positive feedback or whether both are needed. To test this, we used dynamic clamp to inject selected previously recorded trains of GABAergic postsynaptic conductances (PSgs) collected during the different feedback states of the daily surge model into GnRH neurons from OVX, OVX+E AM, and OVX+E PM mice. PSg trains mimicking positive feedback initiated more action potentials in cells from OVX+E PM mice than negative feedback or OVX (open feedback loop) trains in all three animal models, but the positive-feedback train was most effective when applied to cells during positive feedback. In silico studies of model GnRH neurons in which >1000 PSg trains were tested exhibited the same results. These observations support the hypothesis that GnRH neurons integrate fast-synaptic and intrinsic changes to increase firing rates during positive feedback.SIGNIFICANCE STATEMENT Infertility affects 15%-20% of couples; failure to ovulate is a common cause. Understanding how the brain controls ovulation is critical for new developments in both infertility treatment and contraception. Ovarian estradiol alters both the intrinsic properties of gonadotropin-releasing hormone (GnRH) neurons and synaptic inputs to these cells coincident with production of sustained GnRH release that ultimately triggers ovulation. We demonstrate here using dynamic clamp and mathematical modeling that estradiol-induced shifts in synaptic transmission alone can increase firing output, but that the intrinsic properties of GnRH neurons during positive feedback further poise these cells for increased response to higher frequency synaptic transmission. These data suggest that GnRH neurons integrate fast-synaptic and intrinsic changes to increase firing rates during the preovulatory GnRH surge.

Evaluation of Bisphenol A (BPA) Exposures on Prostate Stem Cell Homeostasis and Prostate Cancer Risk in the NCTR-Sprague-Dawley Rat: An NIEHS/FDA CLARITY-BPA Consortium Study.

Background:Previous work determined that early life exposure to low-dose Bisphenol A (BPA) increased rat prostate cancer risk with aging. Herein, we report on prostate-specific results from CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity), which aims to resolve uncertainties regarding BPA toxicity.Objectives:We sought to a) reassess whether a range of BPA exposures drives prostate pathology and/or alters prostatic susceptibility to hormonal carcinogenesis, and b) test whether chronic low-dose BPA targets prostate epithelial stem and progenitor cells.Methods:Sprague-Dawley rats were gavaged daily with vehicle, ethinyl estradiol (EE) or BPA/kg-BW during development or chronically, and prostate pathology was assessed at one year. One developmentally exposed cohort was given testosterone plus estradiol () implants at day 90 to promote carcinogenesis with aging. Epithelial stem and progenitor cells were isolated by prostasphere (PS) culture from dorsolateral prostates (DLP) of rats continuously exposed for six months to BPA/kg-BW. Gene expression was analyzed by quantitative real time reverse transcription polymerase chain reaction (qRT-PCR).Results:Exposure to BPA alone at any dose did not drive prostate pathology. However, rats treated with EE, 2.5, 250, or BPA/kg-BW plus showed greater severity of lateral prostate intraepithelial neoplasia (PIN), and DLP ductal adenocarcinoma multiplicity was markedly elevated in tumor-bearing rats exposed to -BW. DLP stem cells, assessed by PS number, doubled with chronic EE and exposures. PS size, reflecting progenitor cell proliferation, was greater at 25 and BPA doses, which also shifted lineage commitment toward basal progenitors while reducing luminal progenitor cells.Conclusions:Together, these results confirm and extend previous evidence using a rat model and human prostate epithelial cells that low-dose BPA augments prostate cancer susceptibility and alters adult prostate stem cell homeostasis. Therefore, we propose that BPA exposures may contribute to the increased carcinogenic risk in humans that occurs with aging. https://doi.org/10.1289/EHP3953