Hormonal Manipulation Research Articles

The Estrogen Receptor Alpha Regulates the Sex-dependent Expression and Pronociceptive Role of Bestrophin-1 in Neuropathic Rats

Bestrophin-1, a calcium-activated chloride channel (CaCC), is involved in neuropathic pain; however, it is unclear whether it has a dimorphic role in female and male neuropathic rats. This study investigated if 17β-estradiol and estrogen receptor alpha (ERα) activation regulate bestrophin-1 activity and expression in neuropathic rats. Neuropathic pain was induced by L5-spinal nerve transection (SNT). Intrathecal administration of CaCCinh-A01 (.1–1 µg), a CaCC blocker, reversed tactile allodynia induced by SNT in female but not male rats. In contrast, T16Ainh-A01, a selective anoctamin-1 blocker, had an equal antiallodynic effect in both sexes. SNT increased bestrophin-1 protein expression in injured L5 dorsal root ganglia (DRG) in female rats but decreased bestrophin-1 protein in L5 DRG in male rats. Ovariectomy prevented the antiallodynic effect of CaCCinh-A01, but 17β-estradiol replacement restored it. The effect of CaCCinh-A01 was prevented by intrathecal administration of MPP, a selective ERα antagonist, in rats with and without prior hormonal manipulation. In female rats with neuropathy, ovariectomy prevented the increase in bestrophin-1 and ERα protein expression, while 17β-estradiol replacement allowed for an increase in both proteins in L5 DRG. Furthermore, ERα antagonism (with MPP) prevented the increase in bestrophin-1 and ERα protein expression. Finally, ERα activation with PPT, an ERα selective activator, induced the antiallodynic effect of CaCCinh-A01 in neuropathic male rats and prevented the reduction in bestrophin-1 protein expression in L5 DRG. In summary, data suggest ERα activation is necessary for bestrophin-1’s pronociceptive action to maintain neuropathic pain in female rats. PerspectiveThe mechanisms involved in neuropathic pain differ between male and female animals. Our data suggest that ERα is necessary for expression and function of bestrophin-1 in neuropathic female but not male rats. Data support the idea that a therapeutic approach to relieving neuropathic pain must be based on patient's gender.

Tick-tock, racing the clock: parasitism is associated with decreased sprint performance in the Eastern fence lizard

Abstract Host–parasite relationships are important components of ecological systems that influence the evolution of both hosts and parasites. High levels of ectoparasitic infections can disrupt host homeostasis, causing adverse effects on health and performance. However, the effects of natural ectoparasite levels on host physiology are less understood, with most research designs implementing experimental or hormonal manipulations of hosts. In this study, we examined the interplay between tick parasitism and host characteristics on body condition and locomotor performance in Eastern fence lizards in natural settings. We found a higher frequency of tick infections in male lizards relative to females, with larger males being more likely to experience tick infection. Infected lizards had reduced locomotor performance, max sprint speed and 2-m run speed. Together this suggests an energetic trade-off between increased immune function and reduced locomotor performance, which is consistent with the immunocompetence–handicap hypothesis. Higher numbers of ticks on adult male lizards may be explained by age as well as the immunosuppressive effects of testosterone. Tick infection did not appear to reduce overall body condition of lizard hosts. Our findings shed light on the interplay between ectoparasitic infection, host characteristics, and locomotor performance under natural conditions. Such insights are crucial for understanding host–parasite dynamics and determining the trade-offs for hosts within ecological contexts.

How Sex Hormones Affect Migraine: An Interdisciplinary Preclinical Research Panel Review.

Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation, particularly during puberty, pregnancy, and perimenopause. Ovarian steroids, such as estrogen and progesterone, exert complex effects on the peripheral and central nervous systems, including pain, a variety of special sensory and autonomic functions, and affective processing. A panel of basic scientists, when challenged to explain what was known about how sex hormones affect the nervous system, focused on two hormones: estrogen and oxytocin. Notably, other hormones, such as progesterone, testosterone, and vasopressin, are less well studied but are also highlighted in this review. When discussing what new therapeutic agent might be an alternative to hormone therapy and menopause replacement therapy for migraine treatment, the panel pointed to oxytocin delivered as a nasal spray. Overall, the conclusion was that progress in the preclinical study of hormones on the nervous system has been challenging and slow, that there remain substantial gaps in our understanding of the complex roles sex hormones play in migraine, and that opportunities remain for improved or novel therapeutic agents. Manipulation of sex hormones, perhaps through biochemical modifications where its positive effects are selected for and side effects are minimized, remains a theoretical goal, one that might have an impact on migraine disease and other symptoms of menopause. This review is a call to action for increased interest and funding for preclinical research on sex hormones, their metabolites, and their receptors. Interdisciplinary research, perhaps facilitated by a collaborative communication network or panel, is a possible strategy to achieve this goal.

Cardio-oncology in advanced prostate cancer.

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.

Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study.

The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.

Maturation of Female Yellow Rasbora (<i>Rasbora Lateristriata</i> Bleeker, 1854) Using Oodev at Different Doses in Feed

The current high demand for Yellow rasbora (Rasbora lateristriata) is not supported by the availability of captured Yellow rasbora in nature. Aquaculture is the most rational way of utilizing biological natural resources. In intensive aquaculture, it is necessary to optimize all processes that occur in aquaculture, including hatchery. However, the common problem that often happens in hatchery activities is spawning which depends on the season. The hormonal manipulation technique is an appropriate way to stimulate gonadal maturation. Oodev is a hormonal combination of pregnant mare serum gonadotropin and anti-dopamine to stimulate gonadal maturation. The purpose of this study was to determine the effectiveness of using the Oodev with different doses in feed to accelerate gonad maturation of female Yellow rasbora. The study was carried out with four treatments and three replications in 21 days with different doses of Oodev, such as; A (Feed without Oodev), B (0.5 mL/kg feed), C (1 mL/kg feed) and D (2 mL/kg feed). The parameters observed in this study were gonad maturity level, histological structure of ovary, gonadosomatic index, fecundity, and diameter of eggs. The results showed that the dose of Oodev at 1.0 mL/kg feed was an effective dose to optimize the gonad maturity of female Yellow rasbora. This is proven by the highest results shown on all parameters, such as; the maturity level in the IV phase, histological structure of the ovary which showed the dominance of the oocyte maturation phase, gonadosomatic index of 14.014%, the fecundity of 721 eggs, and egg diameter of 0.865 mm. In conclusion, using Oodev in feed at a dose of 1.0 ml/kg of feed for 21 days is an effective dose to optimize the maturation of female Yellow rasbora.

#363 : Kisspeptins and Human Reproduction: New Challenges in the Management of Couple Infertility

Background and Aims: Human reproduction is strictly controlled by a complex neurohormonal system including the gonadotropin-releasing hormone (GnRH) production, which stimulates anterior pituitary gonadotropes secretion and thereby gonadal function. Now, it is well known that GnRH neurons are regulated by Kisspeptins, a family of neuropeptides encoded by the Kiss1 gene and produced mainly in the arcuate and periventricular nuclei of the third ventricle in the hypothalamus. This review aims to provide an updated view in the physiological effects of kisspeptins in male and female reproduction and to highlight future research challenges in therapeutic alternatives for the management of couple infertility. Method: A non-systematic review of the literature was performed by screening PubMed up to April 2023 using the search terms including “Kisspeptin”, “gonadotropin-releasing hormone”, “male infertility”, “female infertility”, “sperm”, “oocyte”, and “Assisted Reproductive Technology”. Results: Many reports suggested the importance of kisspeptins in various aspects of male and female reproduction, from sexual differentiation and puberty onset to adult regulation of gonadotropin secretion and the metabolic control of fertility. Kisspeptin is involved in oocyte development, quality of semen, steroidogenesis in both the ovaries and testes, sexual desires and pregnancy. Recently, a potential clinical relevance of kisspeptins was noted with emerging interests in applied medicine. Some investigations are being carried out to develop these neuromodulators as a diagnostic marker in male and female infertility. Kisspeptin analogs could constitute a new therapeutic strategy based on hormonal manipulation of the hypothalamic-pituitary-gonadal axis. Conclusion: Further clinical trials are needed to provide the required evidence for the use of kisspeptin to trigger reproductive axis, gonadic functions and gametes differentiation guiding future clinical practice in couple infertility.

Primary ovarian insufficiency- An overview: Part 2 diagnosis and management

Loss of normal ovarian function before the age of 40 characterizes primary ovarian insufficiency (POI), sometimes called premature ovarian failure or early menopause. Many women all around the globe deal with this serious reproductive health issue. The purpose of this study is to provide a broad perspective on how to identify and treat primary ovarian insufficiency. Clinical symptoms, hormone profiles, and ovarian imaging all play a role in making a diagnosis of POI. Genetic predisposition, autoimmune disease, and medical intervention are all possible origins. Counseling and treatment techniques for afflicted women can only be used when a timely and correct diagnosis has been made. Hormone replacement treatment (HRT) for symptom alleviation, avoidance of long-term consequences including osteoporosis and cardiovascular disease, and preservation of fertility are all part of the management of postmenopausal irritability (POI). To reduce the severity of menopausal symptoms and safeguard bone health, oestrogen replacement treatment is needed. HRT selection should be patient-specific, taking into account factors like as age, co-morbidities, and individual preferences. If a young woman is diagnosed with POI and she wants to have children in the future, she and her doctor should talk about fertility preservation strategies such oocyte or ovarian tissue cryopreservation. The latest treatments and possible revolutionary methods to POI management are also discussed in this overview. Stem cell therapy, ovarian tissue transplantation, and hormone manipulation are all examples of such unproven methods. While these treatments are still in their infancy, they show promise for the future of POI management. In conclusion, this review article gives a comprehensive, up-to-date explanation of how primary ovarian insufficiency is diagnosed and treated. Early detection, proper counselling, and individualised treatment plans are emphasised for afflicted females. The reproductive and overall health results of these people may be improved with a deeper knowledge of the processes producing POI and the development of more effective medicines.

Differential early‐life survival underlies the adaptive significance of temperature‐dependent sex determination in a long‐lived reptile

Abstract Many ectotherms rely on temperature cues experienced during development to determine offspring sex. The first descriptions of temperature‐dependent sex determination (TSD) were made over 50 years ago, yet an understanding of its adaptive significance remains elusive, especially in long‐lived taxa. One novel hypothesis predicts that TSD should be evolutionarily favoured when two criteria are met—(a) incubation temperature influences annual juvenile survival and (b) sexes mature at different ages. Under these conditions, a sex‐dependent effect of incubation temperature on offspring fitness arises through differences in age at sexual maturity, with the sex that matures later benefiting disproportionately from temperatures that promote juvenile survival. The American alligator (Alligator mississippiensis) serves as an insightful model in which to test this hypothesis, as males begin reproducing nearly a decade after females. Here, through a combination of artificial incubation experiments and mark‐recapture approaches, we test the specific predictions of the survival‐to‐maturity hypothesis for the adaptive value of TSD by disentangling the effects of incubation temperature and sex on annual survival of alligator hatchlings across two geographically distinct sites. Hatchlings incubated at male‐promoting temperatures (MPTs) consistently exhibited higher survival compared to those incubated at female‐promoting temperatures. This pattern appears independent of hatchling sex, as females produced from hormone manipulation at MPT exhibit similar survival to their male counterparts. Additional experiments show that incubation temperature may affect early‐life survival primarily by affecting the efficiency with which maternally transferred energy resources are used during development. Results from this study provide the first explicit empirical support for the adaptive value of TSD in a crocodilian and point to developmental energetics as a potential unifying mechanism underlying persistent survival consequences of incubation temperature. Read the free Plain Language Summary for this article on the Journal blog.

Central regulation of stress-evoked peripheral immune responses.

Stress-linked psychiatric disorders, including anxiety and major depressive disorder, are associated with systemic inflammation. Recent studies have reported stress-induced alterations in haematopoiesis that result in monocytosis, neutrophilia, lymphocytopenia and, consequently, in the upregulation of pro-inflammatory processes in immunologically relevant peripheral tissues. There is now evidence that this peripheral inflammation contributes to the development of psychiatric symptoms as well as to common co-morbidities of psychiatric disorders such as metabolic syndrome and immunosuppression. Here, we review the specific brain and spinal regions, and the neuronal populations within them, that respond to stress and transmit signals to peripheral tissues via the autonomic nervous system or neuroendocrine pathways to influence immunological function. We comprehensively summarize studies that have employed retrograde tracing to define neurocircuits linking the brain to the bone marrow, spleen, gut, adipose tissue and liver. Moreover, we highlight studies that have used chemogenetic or optogenetic manipulation or intracerebroventricular administration of peptide hormones to control somatic immune responses. Collectively, this growing body of literature illustrates potential mechanisms through which stress signals are conveyed from the CNS to immune cells to regulate stress-relevant behaviours and comorbid pathophysiology.

The Effect of Immersion Duration of java barb larvae (Barbornymus gonionotus) in the combination of thyroxine hormone and recombinant growth hormone (rGH) on the egg yolk absorption and growth

Java barb (Tawes) is one of the endemic freshwater fish in Indonesia which has being widely cultivated. The time rearing of Java barb from larva to market size is generally 5-6 months. Egg yolk absorption rate and growth of Java barb fish can be increased by hormonal manipulation using thyroxine hormone and recombinant growth hormone (rGH). The length of immersion time affects the performance of hormones in the fish’s body. The purpose of this study is to determine the effect of immersion duration and the best immersion time in a combination of thyroxine and rGH on the egg yolk absorption and the growth of Java barb larvae. This research was conducted on 23 August-1 November 2021 at Laboratorium Pengujian Kesehatan Ikan dan Lingkungan (LPKIL) in Muntilan, Magelang regency. The testing fishes used were early hatched Java barb fish larvae that still had egg yolks. The method used was a completely random design (CRD) with 4 treatments and 3 replications and each was done with a combination of 0.1 mg/l thyroxine hormone and 2.5 mg/l rGH with treatments A (control), B (1 hour immersion time), C (2 hours immersion time) and D (3 hours immersion time). The results showed that the effect of immersion duration in combination of thyroxine and rGH had a significant effect on the rate of egg yolk absorption and the growth of Java barb fish larvae. The best immersion time was treatment D (3 hours immersion duration) which resulted in 4%/hour of the absorption rate of egg yolk absorption rate, 12.53±0.15 mm absolute length growth, 0.047±0.002 g absolute weight growth, 13.82±0.15 % of specific growth rate, and 54.67±4.62 % survival rate.

Unraveling the Mechanisms of Virus-Induced Symptom Development in Plants.

Plant viruses, as obligate intracellular parasites, induce significant changes in the cellular physiology of host cells to facilitate their multiplication. These alterations often lead to the development of symptoms that interfere with normal growth and development, causing USD 60 billion worth of losses per year, worldwide, in both agricultural and horticultural crops. However, existing literature often lacks a clear and concise presentation of the key information regarding the mechanisms underlying plant virus-induced symptoms. To address this, we conducted a comprehensive review to highlight the crucial interactions between plant viruses and host factors, discussing key genes that increase viral virulence and their roles in influencing cellular processes such as dysfunction of chloroplast proteins, hormone manipulation, reactive oxidative species accumulation, and cell cycle control, which are critical for symptom development. Moreover, we explore the alterations in host metabolism and gene expression that are associated with virus-induced symptoms. In addition, the influence of environmental factors on virus-induced symptom development is discussed. By integrating these various aspects, this review provides valuable insights into the complex mechanisms underlying virus-induced symptoms in plants, and emphasizes the urgency of addressing viral diseases to ensure sustainable agriculture and food production.

Temporal dynamics of neurobehavioral hormone sensitivity in a scaled-down experimental model of early pregnancy and parturition.

The hormonal changes of pregnancy and parturition can trigger robust changes in affective state, particularly among patients with a history of postpartum depression. However, more work is needed to elucidate the temporal dynamics of symptom emergence. The current study explored how quickly hormone-sensitive (HS+) individuals can be differentiated from hormone-insensitive (HS-) controls in the context of a tightly controlled experimental hormone manipulation, and which symptoms demonstrate the most rapid, consistent, and largest response during this protocol. Participants were female, non-pregnant, and euthymic, with a history of DSM-5 major depressive episode with peripartum onset (n = 15) or parous healthy controls with no psychiatric history (n = 15). Perinatal hormonal changes were simulated by inducing hypogonadism, adding back estradiol (E2) and progesterone (P4) to reach first-trimester levels for 8 weeks, and then subsequently withdrawing both hormones. Those reporting a 30% or greater increase during addback or withdrawal on select subscales of the Inventory of Depression and Anxiety Symptoms (IDAS) were identified as HS+. Participants provided daily ratings of symptoms throughout the study via the Daily Record of Severity of Problems. Results indicated that HS+ participants could be differentiated from HS- participants early in the hormone protocol, with many symptoms showing significantly greater change from baseline within the first week of addback. Notably, the most rapid symptom increases were observed for Anger/Irritability, Mood Swings, Overwhelm, Lethargy, Increased Appetite, Joint and Muscle Pain, and Breast Tenderness, reaching 50% of peak group contrast within the first week of hormone addback. The largest group effects were observed for Anger/Irritability, followed by Fatigue and Anxiety, and the most consistent group effects were observed for Anger/Irritability, Interpersonal Conflict, Overwhelm, and Hopelessness. Findings support the role of reproductive hormones in the onset of perinatal affective disorders. The rapid emergence of anger and irritability in HS+ participants suggests that these symptoms may be early indicators of perinatal hormone sensitivity.

Male infertility and urological tumors: Pathogenesis and therapeutical implications.

Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and penis are diagnosed early and treated in relatively younger patients in which couple fertility can be an important concern. The purpose of this review is to highlight both the pathogenetic mechanisms of damage to male fertility in the context of the main urological cancers and the methods of preserving male fertility in an oncological setting, in light of the most recent scientific evidence. A systematic review of available literature was carried out on the main scientific search engines, such as PubMed, Clinicaltrials.Gov, and Google scholar. Three hundred twenty-five relevant articles on this subject were identified, 98 of which were selected being the most relevant to the purpose of this review. There is a strong evidence in literature that all of the genitourinary oncological therapies have a deep negative impact on male fertility: orchiectomy, partial orchiectomy, retroperitoneal lymphadenectomy (RPLND), radical cystectomy, prostatectomy, penectomy, as well as radiotherapy, chemotherapy, and hormonal androgen suppression. Preservation of fertility is possible and includes cryopreservation, hormonal manipulation with GnRH analogs before chemotherapy, androgen replacement. Germ cell auto transplantation is an intriguing strategy with future perspectives. Careful evaluation of male fertility must be a key point before treating genitourinary tumors, taking into account patients' age and couples' perspectives. Informed consent should provide adequate information to the patient about the current state of his fertility and about the balance between risks and benefits in oncological terms. Standard approaches to genitourinary tumors should include a multidisciplinary team with urologists, oncologists, radiotherapists, psycho-sexologists, andrologists, gynecologists, and reproductive endocrinologists.

Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and nonusers.

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and DA release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater DA synthesis capacity than NC participants, particularly in dorsal caudate, and greater cognitive flexibility. Furthermore, across individuals, the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or DA release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to women's hormone status. Hormonal contraception (in the form of pill, shot, implant, ring, or intrauterine device) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the DA system. Findings from this study begin to address this critical gap in women's health.

Thyroid hormone manipulation influences development of endothermy and hatching in white leghorn chickens (Gallus gallus)

Chickens experience rapid change in their physiology and metabolism during hatching. We propose that thyroid hormones play a major role in regulating the developmental changes associated with attaining endothermy. To better understand the role thyroid hormones play in hatch timing and development of thermogenic capacity and metabolic rate we manipulated plasma thyroid hormone levels in chicken embryos beginning at 80% development (day 17 of a 21-day incubation) with either a single dose of triiodo-L-thyronine (T3) or the thyroperoxidase inhibitor methimazole (MMI). Manipulation of thyroid hormones altered the timing of hatching, accelerating hatching under hyperthyroid conditions, and prolonging hatching with hypothyroid conditions. Effect sizes comparisons of morphological variables between treatment groups revealed larger heart and body masses in hyperthyroid 1-day post hatch animals. Thyroid hormone manipulation influenced the thermal neutral zone for O2 consumption and body temperature during gradual cooling from 35 to 15 °C of externally pipped embryos and 1-day post hatch chicks. Hyperthyroid EP animals had a wider thermal neutral zone during cooling when compared to control animals. At the temperatures tested, the hypothyroid animals did not exhibit a thermal neutral zone. Similar differences between treatments in the breadth of the thermal neutral zone carried through to 1-day post hatch chickens. These findings suggest that thyroid manipulations influence the timing and development of the animal’s thermogenic response to cooling.

Review: Manipulation of follicle development to improve fertility of cattle in timed-artificial insemination programs.

The development of an ovulatory follicle is a fundamental premise for any reproductive management program that aims to optimize fertility in cattle. Controlling follicular development comprises the synchronized emergence of a new follicular wave, selection and growth of the dominant follicle, and synchronized ovulation of a high-quality oocyte. All these follicular events, primarily driven by gonadotropin secretion, occur under a very dynamic hormonal environment. In this sense, controlling follicular development demands essentially a precise manipulation of the hormonal environment to modulate gonadotropin secretion. Furthermore, the effectiveness of hormonal manipulation strategies in the management of follicular development depends on specific particularities of each situation, which can vary widely according to genetic groups (Bos taurus vs Bos indicus), nutritional, metabolic, and reproductive status. In this regard, the constant search for the refined synchrony between the hormonal treatments and reproductive events, considering these distinctions and particularities, have provided valuable information that contributed to the development of efficient reproductive programs. This manuscript discusses the physiological bases behind the development of fine-tuned timed-artificial insemination protocols for beef and dairy cattle that resulted in great improvements in reproductive efficiency of beef and dairy herds.

Evaluations of memory, anxiety, and the growth factor IGF-1R after post-surgical menopause treatment with a highly selective progestin

Progestogens are a key component of menopausal hormone therapies. While some progestogens can be detrimental to cognition, there is preclinical evidence that progestogens with a strong progesterone-receptor affinity benefit some molecular mechanisms believed to underlie cognitive function. Thus, a progestin that maximizes progesterone-receptor affinity and minimizes affinities to other receptors may be cognitively beneficial. We evaluated segesterone-acetate (SGA), a 19-norprogesterone derivative with a strong progesterone-receptor affinity and no androgenic or estrogenic-receptor activity, hypothesizing that it would enhance cognition. Middle-aged rats underwent Sham or Ovariectomy (Ovx) surgery followed by administration of medroxyprogesterone-acetate (MPA; used as a positive control as we have previously shown MPA-induced cognitive deficits), SGA (low or high dose), or vehicle (one Sham and one Ovx group). Spatial working and reference memory, delayed retention, and anxiety-like behavior were assessed, as were memory- and hormone- related protein assays within the frontal cortex, dorsal hippocampus, and entorhinal cortex. Low-dose SGA impaired spatial working memory, while high-dose SGA had a more extensive detrimental impact, negatively affecting spatial reference memory and delayed retention. Replicating previous findings, MPA impaired spatial reference memory and delayed retention. SGA, but not MPA, alleviated Ovx-induced anxiety-like behaviors. On two working memory measures, IGF-1R expression correlated with better working memory only in rats without hormone manipulation; any hormone manipulation or combination of hormone manipulations used herein altered this relationship. These findings suggest that SGA impairs spatial cognition after surgical menopause, and that surgical menopause with or without progestin administration disrupts relationships between a growth factor critical to neuroplasticity.

Abstract P3-05-29: Use of Bioimpedance Spectroscopy as a Surrogate for Bone Mineral Content in Oncology Patients: Practical Application of the SOZO Device

Abstract Background: Many cancer patients, particularly those with breast or prostate cancer, receive hormonal manipulation therapies that can significantly impact their bone mineral content (BMC), potentially leading to osteoporotic associated life-threatening fractures, particularly given the median age of patients diagnosed with these malignancies. Bioimpedance spectroscopy (BIS) is a non-invasive tool that measures fluid and body composition values including skeletal muscle mass (SMM) and fat free mass (FFM). BIS devices can be used easily and quickly at point-of-care at the time of vital signs, with the patient standing on the device placing their hands and feet on metal electrodes and a reading obtained in less than a minute. Multiple previous studies have shown strong correlation between SMM and BMC, suggesting that a BIS reading can provide a reproducible, simple and quick estimate of BMC. To that end, we present initial findings correlating BIS readings obtained with a SOZO device (ImpediMed) with dual x-ray absorptiometry (DXA) to determine if BIS readings can be applied as an accurate point of care surrogate measure of BMC. Materials and Methods: Concurrent BIS measures and DXA scans, were performed in 75 healthy volunteers and 93 cancer patients (during and after cancer treatment) Group 1: 75 healthy volunteers (32 male, 43 female), mean age 27.4 (18-66 years); Group 2: 44 patients undergoing cancer treatment (11 male, 33 female; 18 breast, 7 lung, 4 endometrial, 4 colorectal, 4 prostate, 7 other), mean age 61.3 (38-79 years); and Group 3: 49 patients participating in a 12-week exercise program after cancer treatment (15 males, 34 females; 22 breast, 6 prostate, 3 colorectal, 3 endometrial, 2 lung, 13 other), mean age 57.8 (19-79 years). The healthy volunteers in Group 1 were further randomized into two subsets. Group A was used to develop a BIS predicted BMC algorithm and Group B was used to validate the algorithm. Results: The Pearson correlation coefficients (R) for DXA BMC and SOZO SMM were strong for all 3 groups (R=0.92, 0.85, and 0.80 for Groups 1, 2, and 3, respectively). Stepwise multiple linear regression for BMC was performed for Group A based on BIS parameters. For Group A, SMM resulted in a multiple correlation coefficient of 0.94 (P< 0.0001). The correlation coefficient between the BIS predicted BMC and DXA BMC of Group B was 0.87 (P< 0.0001, 95%CI 0.78-0.93). For Groups 2 and 3 combined, the correlation coefficient between the BIS predicted BMC and DXA BMC was 0.82 (P< 0.0001, 95%CI 0.73-0.87). Conclusions: Concurrent measures of SMM obtained with BIS using SOZO correlated strongly with DXA BMC, demonstrating that SOZO SMM may be a useful surrogate in the clinic to provide a quick, easy, and reproducible indicator of change in BMC, particularly for those patients undergoing treatments that may affect BMC. Tracking SMM during or after cancer treatment with SOZO may provide an estimate of changes in BMC allowing clinicians to obtain additional diagnostic testing and/or consider treatment modifications. Citation Format: Frank Vicini, Chirag Shah. Use of Bioimpedance Spectroscopy as a Surrogate for Bone Mineral Content in Oncology Patients: Practical Application of the SOZO Device [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-29.

Biocompatible polymeric microparticles serve as novel and reliable vehicles for exogenous hormone manipulations in passerines

The administration of exogenous hormones emerged as an essential tool for field studies in endocrinology. However, working with wild animals remains challenging, because under field conditions not every available method meets the necessary requirements. Achieving a sustained elevation in hormone levels, while simultaneously minimising handling time and invasiveness of the procedure is a difficult task in field endocrinology.Facing this challenge, we have investigated the suitability of biocompatible polymeric microparticles, a novel method for drug-administration, as a tool to manipulate hormones in small songbirds. We chose the insulin-like growth factor-1 (IGF-1) as target hormone, because it receives great interest from the research community due to its important role in shaping life-history traits. Moreover, its short half-life and hydrophilic properties imply a major challenge in finding a suitable method to achieve a sustained, systemic long-term release. To study the release kinetics, we injected either IGF-1 loaded polylactic-co-glycolic acid (PLGA) microparticles or dispersion medium (control group) in the skin pocket of the interscapular region of captive bearded reedlings (Panurus biarmicus). We collected blood samples for 7 consecutive days plus an additional sampling period after two weeks and complemented these with an in vitro experiment.Our results show that in vitro, PLGA microparticles allowed a stable IGF-1 release for more than 15 days, following a burst release at the beginning of the measurement. In vivo, the initial burst was followed by a drop to still elevated levels in circulating IGF-1 until the effect vanished by 16 days post-treatment.This study is the first to describe the use of PLGA-microparticles as a novel tool for exogenous hormone administration in a small passerine. We suggest that this method is highly suitable to achieve the systemic long-term release of hydrophilic hormones with short half-life and reduces overall handling time, as it requires only one subcutaneous injection.