Stimulating Luteinizing Hormone Research Articles

Long-term effect of exposure to triethylene glycol dimethacrylate (TEGDMA) on male mouse reproduction.

Our study investigated the impact on male mouse fertility and reproduction of long-term (14 weeks) exposure to triethylene glycol dimethacrylate (TEGDMA), a co-monomer of resin-based compounds, at doses of 0.01, 0.1, 1, and 10ppm. Test and control mice were then paired with sexually mature untreated female mice and their fertility evaluated. Females paired with males exposed to all TEGDMA doses exhibited a significant decline in pregnancy rates, and significant increases in the total embryonic resorption-to-implantation ratio, except for males exposed to 0.01ppm TEGDMA. Males in the highest dose group (10ppm) showed significant increases in seminal vesicle and preputial gland weights. They also had significantly higher serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) than the controls, and the 0.01ppm dosage group for FSH levels. TEGDMA exposure resulted in notable histopathological alterations in the testis, with detachment of germ cells and shedding of germinal epithelium into the tubule lumen. These results strongly indicate that TEGDMA exposure has detrimental consequences on the reproductive abilities and functions in male mice through disruption of the standard hormonal regulation of the reproductive system, leading to changes in spermatogenesis and ultimately leading to decreased fertility.

Reflex strategy to ensure accurate total testosterone results from consumer initiated, self-collected capillary samples

BackgroundSelf-collected capillary samples are convenient for direct access testing (DAT), but exogenous testosterone use may cause falsely elevated total testosterone (TT) results.We designed a quality assurance workflow to differentiate between accurate or erroneous supraphysiological TT concentrations. MethodsClinical samples with TT > 1500 ng/dL were reflexed to luteinizing hormone (LH) and follicle stimulating hormone (FSH) and screened for exogenous testosterone use. Samples (n = 120) with normal TT were reflexed to LH/FSH as a control. ResultsA total of 8572 TT samples were evaluated, of which 533 (6.2 %) had TT > 1500 ng/dL and were reflexed. Of these, 441 (82.7 %) had significantly decreased LH/FSH (<0.85/<0.7mIU/mL, respectively), 72 (13.5 %) had normal or borderline normal LH/FSH, and 20 (3.8 %) had insufficient plasma volume. In patients with TT > 1500 ng/dL, injectable exogenous testosterone use was most commonly accompanied by significantly decreased LH/FSH, while topical testosterone use was most commonly accompanied by detectable LH/FSH. Control samples were almost all (99.2 %) within or above the LH/FSH reference intervals. Unique patients ordered 351 TT tests where at least one TT result was > 1500 ng/dL. Based on TT and LH/FSH results, we hypothesized that patients were intermittently or consistently overusing exogenous testosterone, resolved elevated TT with recollection, or repeatedly contaminated their sample. ConclusionSelf-collected capillary specimens are acceptable for TT testing. A quality assurance reflex to LH/FSH can determine the validity of supraphysiological TT results in a consumer initiated/DAT population.

Protective effect of selenomethionine on rabbit testicular injury induced by Aflatoxin B1

The aim of this study was to investigate the alleviating effect of selenomethionine (SeMet) on aflatoxin B1 (AFB1)-induced testicular injury in rabbits. Twenty-five 90-d-old rabbits were randomly divided into 5 groups (the control group, the AFB1 group, the 0.2 mg/kg SeMet + AFB1 group, the 0.4 mg/kg SeMet + AFB1 group and the 0.6 mg/kg SeMet + AFB1 group). After 1 d of the experiment, the SeMet-treated groups were fed 0.2 mg/kg SeMet, 0.4 mg/kg SeMet, or 0.6 mg/kg SeMet daily, and the remaining two groups were fed a normal diet for 30 d. On Day 31, all rabbits in the model group and the three treatment groups were fed 0.5 mg/kg AFB1 for 21 d. The levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in rabbit plasma were detected. Rabbit semen was collected, and its quality was evaluated. Pathological changes in rabbit testes were observed by hematoxylin-eosin (HE) staining. The expression of related proteins in testicular tissue was detected by immunohistochemistry, immunofluorescence and western blot (WB) analysis. Enzyme-linked immunosorbent assays (ELISAs) were used to detect oxidative stress-related indices and inflammatory factors in testicular tissue. The results showed that AFB1 can induce oxidative stress and inflammation to activate the p38/MSK/NF-κB signalling pathway, mediate apoptosis, inhibit the proliferation and differentiation of testicular cells, destroy the integrity of the blood–testis barrier (BTB) and the normal structure of the testis, and reduce the content of sex hormones and semen quality. SeMet pretreatment significantly alleviated testicular injury oxidative stress, and the inflammatory response in rabbits. Thus, we demonstrated that SeMet restores AFB1-induced testicular toxicity by inhibiting the p38/MSK/NF-κB signalling pathway. In addition, in this study, 0.4 mg/kg SeMet had the most impactful effect.

Central MOTS-c infusion affects reproductive hormones in obese and non-obese rats

MOTS-c, a mitochondrial-derived peptide, acts as a systemic hormone and MOTS-c level is inversely correlated with markers of obesity. Obesity is a risk factor for male reproductive physiology and is expressed as an important cause of infertility. In this study, we aimed to determine the effects of MOTS-c, which has been proven in the hypothalamus and testicles, on the actors involved in the reproductive axis.In the study, 80 male Wistar-Albino rats were divided into two main groups, obese and non-obese (n = 40). Rats in the first main group were fed with fatty diet feed and obesity was induced. The second main group was fed with normal diet feed. Each main group was divided into 4 subgroups (Control, Sham, 10 and 100 µM MOTS-c). The lateral ventricles of the animals in the treatment groups were infused with 10 and 100 µM MOTS-c (solvent in Sham group) for 14 days. At the end of the experiment, hypothalamic Gonadotropin-Releasing Hormone (GnRH) gene expression level, serum testosterone, Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels were determined.MOTS-c infusion caused an increase in GnRH mRNA, protein expression levels and serum testosterone, LH and FSH levels in obese and non-obese rats (p < 0.05). MOTS-c administration more significantly upregulated hormone levels in non-obese rats (p < 0.05). MOTS-c administration increases these hormones, suggesting that MOTS-c may stimulate the reproductive axis.Our results reveal that MOTS-c plays a role in the central regulation of reproduction, as well as causes increased LH, FSH and testosterone release.

HormoneBayes: A novel Bayesian framework for the analysis of pulsatile hormone dynamics.

The hypothalamus is the central regulator of reproductive hormone secretion. Pulsatile secretion of gonadotropin releasing hormone (GnRH) is fundamental to physiological stimulation of the pituitary gland to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). Furthermore, GnRH pulsatility is altered in common reproductive disorders such as polycystic ovary syndrome (PCOS) and hypothalamic amenorrhea (HA). LH is measured routinely in clinical practice using an automated chemiluminescent immunoassay method and is the gold standard surrogate marker of GnRH. LH can be measured at frequent intervals (e.g., 10 minutely) to assess GnRH/LH pulsatility. However, this is rarely done in clinical practice because it is resource intensive, and there is no open-access, graphical interface software for computational analysis of the LH data available to clinicians. Here we present hormoneBayes, a novel open-access Bayesian framework that can be easily applied to reliably analyze serial LH measurements to assess LH pulsatility. The framework utilizes parsimonious models to simulate hypothalamic signals that drive LH dynamics, together with state-of-the-art (sequential) Monte-Carlo methods to infer key parameters and latent hypothalamic dynamics. We show that this method provides estimates for key pulse parameters including inter-pulse interval, secretion and clearance rates and identifies LH pulses in line with the widely used deconvolution method. We show that these parameters can distinguish LH pulsatility in different clinical contexts including in reproductive health and disease in men and women (e.g., healthy men, healthy women before and after menopause, women with HA or PCOS). A further advantage of hormoneBayes is that our mathematical approach provides a quantified estimation of uncertainty. Our framework will complement methods enabling real-time in-vivo hormone monitoring and therefore has the potential to assist translation of personalized, data-driven, clinical care of patients presenting with conditions of reproductive hormone dysfunction.

Could polyphenols be an effective treatment in the management of polycystic ovary syndrome?

Polycystic ovary syndrome (PCOS), is a health problem observed in women of reproductive age. Different diets, physical activity recommendations and lifestyle changes can be effective in dealing with the symptoms of PCOS. Nutrition is indeed an essential part of the treatment of the disease as it directly affects body weight loss, insulin resistance, lipid profile, hormones, and dermatological complaints such as acne. Polyphenols, simply classified as flavonoids and non-flavonoids, are bioactive components found in plant-based foods. The most common polyphenols in the diet are flavanols, flavonols, flavanone, anthocyanins. In particular, polyphenols which are compounds naturally found in foods, have antioxidant, anticancer, anti-inflammatory, antimutagenic benefits along with many other ones. In the treatment of PCOS, polyphenols may help reduce the symptoms, improve insulin resistance and poor lipid profile, and cure hormonal disorders. It has been reported that polyphenols are influential in menstrual cycle disorders and enable a decrease in body weight, hyperandrogenism, estrogen, testosterone, luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratios and LH. For adequate daily intake of polyphenols, which are found in high amounts in fruits and vegetables, at least 5 portions of fruits and vegetables should be consumed in addition to a healthy nutrition pattern. In this review, the effects of various polyphenols on polycystic ovary syndrome are discussed.

Comparative studies on the chemical composition and pharmacological effects of vinegar-processed antler glue modified from Lei Gong Pao Zhi Lun and traditional water-processed antler glue

Ethnopharmacological relevanceAntler glue is a classic medicinal to enhance sexual function in traditional Chinese medicine (TCM), which was first recorded in Shen Nong Ben Cao Jing (Shennong′s Classic of the Materia Medica). Vinegar-processing is a classic method of processing traditional Chinese medicine. The method of preparing antler glue by boiling antlers in vinegar and then concentrating them is recorded in Lei Gong Pao Zhi Lun (Master Lei′s Discourse on Medicinal Processing). In modern times, the typical processing method of antler glue is water extraction and concentration. However, it is not clear whether there is a difference in the effect of these two processing methods on the chemical composition and pharmacological activity of antler glue. Aim of the studyThe Chinese Pharmacopoeia (2020) records that the processing method of antler glue is water extraction and concentration. But Lei Gong Pao Zhi Lun differs in Chinese Pharmacopoeia (2020), which records the processing method of vinegar extraction and concentration. The effect of the two processing methods on antler glue's chemical composition and pharmacological activity is unknown. So this study aimed to elucidate the difference between different processing methods on the chemical composition and the treatment effect on oligoasthenospermia of antler glue. Materials and methodsSo the automatic amino acid analyzer is used to determine the amino acid content of two different processing methods of antler glue. Proteomics was performed to detect the protein components of two different processing methods of antler glue and analyze them. Cyclophosphamide-induced mice models of oligoasthenospermia were used to study the different pharmacological effects of antler glue in two different processing methods. An automatic sperm analyzer observed the quantity and quality of sperm in mice epididymis. Serum sex hormone testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in mice were tested using the enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin-eosin (H&E) staining was used to analyze pathological alterations in mouse testicular tissue. The transcriptome has been used to reveal the potential mechanism of antler glue in treating oligoasthenospermia. Mitochondrial complex activity assay kits were used to assay the activity of mitochondrial respiratory chain complex I–V in mouse testicular tissue. Western blot was used to determine the expression of related proteins in mouse testicular tissue. ResultsVinegar-processing can increase the alanine, proline, and glycine content in antler glue, reduce the length of protein peptides in antler glue, and produce a variety of unique proteins. Vinegar-processed antler glue (VAG) increased sperm density, sperm survival, sperm viability, and serum sex hormone levels in oligozoospermic mice. It reversed testicular damage caused by cyclophosphamide, and the effects were differently superior to those of water-processed antler glue (WAG). In addition, transcriptomics and related experiments have shown that VAG can increase the expression of Ndufa2, Uqcr11, Cox6b1, and Atp5i genes and proteins in mouse testis, thus promoting adenosine diphosphate (ATP) synthesis by increasing the activity of mitochondrial respiratory chain complexes I, III, IV and V. By promoting the oxidative phosphorylation process to produce more ATP, VAG can achieve the therapeutic effect of oligoasthenospermia. ConclusionVinegar-processing method can increase the content of active ingredients in antler glue. VAG increases ATP levels in the testes by promoting the process of oxidative phosphorylation to treat oligozoospermia.

Pinostrobin, a dietary bioflavonoid exerts antioxidant, anti-inflammatory, and anti-apoptotic protective effects against methotrexate-induced ovarian toxicity in rats

This study investigated the protective activities of pinostrobin (PIN) against methotrexate (MTX)-induced ovarian toxicity. Female rats were administered with PIN (50 mg/kg) for 4 weeks, while MTX was administered from weeks 2–4 of PIN treatment. Serum hormonal profiles, ovarian oxidative stress, inflammatory and apoptotic biomarkers as well as ovarian histomorphometry were evaluated. MTX administration elicited profound deficit in serum progesterone and estrogen (E2) levels, while luteinizing hormone (LH) and follicle stimulating hormone (FSH) were significantly increased. Additionally, MTX administration was associated with significant increases in ovarian malondialdehyde, nitric oxide, NF-кB, TNF-α, IL-6, IL-1β, iNOS and caspase-3 activity, as well as notable reduction in the activities of glutathione peroxidase, catalase and superoxide dismutase as well as the level of glutathione. Whereas, treatment with PIN significantly decreased serum levels of FSH and LH, as well as ovarian levels of NO, MDA, caspase 3, NF-κB, IL-1β, IL-6, TNF-α and iNOS. PIN also significantly upregulated GSH, GPx, CAT and SOD in the ovarian tissues as well as increased serum E2 and progesterone levels compared to the MTX group. Furthermore, PIN significantly restored altered ovarian histoarchitecture in the treated group. These findings suggests that PIN exerts protective effects against MTX-triggered ovarian damages.

Luteinizing hormone stimulates ingression of mural granulosa cells within the mouse preovulatory follicle†.

Luteinizing hormone (LH) induces ovulation by acting on its receptors in the mural granulosa cells that surround a mammalian oocyte in an ovarian follicle. However, much remains unknown about how activation of the LH receptor modifies the structure of the follicle such that the oocyte is released and the follicle remnants are transformed into the corpus luteum. The present study shows that the preovulatory surge of LH stimulates LH receptor-expressing granulosa cells, initially located almost entirely in the outer layers of the mural granulosa, to rapidly extend inwards, intercalating between other cells. The cellular ingression begins within 30 min of the peak of the LH surge, and the proportion of LH receptor-expressing cell bodies in the inner half of the mural granulosa layer increases until the time of ovulation, which occurs at about 10h after the LH peak. During this time, many of the initially flask-shaped cells appear to detach from the basal lamina, acquiring a rounder shape with multiple filipodia. Starting at about 4h after the LH peak, the mural granulosa layer at the apical surface of the follicle where ovulation will occur begins to thin, and the basolateral surface develops invaginations and constrictions. Our findings raise the question of whether LH stimulation of granulosa cell ingression may contribute to these changes in the follicular structure that enable ovulation.

FRI333 Neurosarcoidosis Induced Panhypopituitarism​

Abstract Disclosure: K. Alfares: None. H. Jeong Han: None. S. Athimulam: None. Introduction: We hereby present a rare case of neurosarcoidosis causing panhypopituitarism. According to Martin-Grace et al who conducted a literature search for the timeframe of 2002 to 2014, there were only 8 cases of neurosarcoidosis associated pan hypopituitarism. Case Report: A 35-year-old male with a known diagnosis of sarcoidosis on skin biopsies presented to the hospital for altered mental status, hypernatremia, hypotension and hypothermia. He reported symptoms of polyuria and polydipsia for several weeks prior to admission. MRI of the brain revealed a 3cm mass in the suprasellar region involving the hypothalamus and bilateral optic tracts with mass effect on the anterior third ventricle. No discrete pituitary or stalk lesion was identified. A ventriculostomy tube was placed for developing hydrocephalus. Biopsy of the suprasellar mass revealed non-caseating granuloma, confirming neurosarcoidosis. Laboratory work up revealed elevated serum sodium at 167 mmol/L, high serum osmolality at 381 mOsm/kg and low urine osmolality at 381 mOsm/kg, consistent with diabetes insipidus. Anterior pituitary hormone profile work up revealed low 8am serum cortisol (1.9 mcg/dL) and inappropriately normal ACTH (34 pg/ml), low serum free testosterone (&amp;lt;2.5 ng/dL) and low Luteinizing hormone (0.7 mIU/ml) and low follicular stimulating hormone (&amp;lt; 2.6 mIU/ml), low free T4 at 0.4 ng/dL and inappropriately normal TSH at 2.77 uIU/mL. Serum prolactin was mildly elevated at 86.8ng/mL. Angiotensin converting enzyme level was within normal range at 33 U/L. A diagnosis of panhypopituitarism was made. Treatment was initiated with high dose IV corticosteroids for management of secondary adrenal insufficiency and neurosarcoidosis. He was also started on IV desmopressin and IV levothyroxine for management of his panhypopituitarism. He was transitioned to oral therapy on discharge. Discussion: Panhypopituitarism secondary to neurosarcoidosis is a rare presentation. Panhypopituitarism from sarcoidosis can occur due to infiltration of the pituitary gland or infiltration of the hypothalamus affecting the hypothalamic-pituitary axis. Sarcoidosis should be considered a differential when evaluating patients with symptoms consistent with panhypopituitarism. Prompt diagnosis and initiation of corticosteroids and deficient hormones can be lifesaving. Presentation: Friday, June 16, 2023

FRI376 Regulation Of Theca Cell Function By Salt-Inducible Kinases

Abstract Disclosure: M. Rodriguez Esquivel: None. E. Hayes: None. O. Lakomy: None. M. Hassan: None. R. Filzen: None. C.O. Stocco: Grant Recipient; Self; NIH R01HD097202. The most common identifiable factors of female infertility are ovulatory disorders. Ovulation is the pinnacle of folliculogenesis, a process that requires an interplay between the oocyte, the granulosa cells, and the theca cells (TCs). TCs are the only source of ovarian androgens. Androgens play vital roles in female fertility acting as substrates for estrogen production in granulosa cells and directly regulating ovarian function via the activation of the androgen receptor. However, abnormally elevated androgen levels reduce fertility in humans and animals, suggesting that a delicate equilibrium exists between the beneficial and harmful effects of androgens in the ovary. Therefore, uncovering novel mechanisms regulating androgen synthesis in TCs is of great significance. The capacity of TCs to synthesize androgens relies on the expression of the rate-limiting enzyme CYP17A1, which converts progestogens into androgens, and its stimulation by the luteinizing hormone (LH). Previously, our group showed that salt-inducible kinases (SIKs) regulate granulosa cell steroidogenesis. Here, we investigated whether SIKs play any role in the regulation of androgen production in TCs. SIK2 and SIK3 were detected by IHC in the TCs of rat ovaries. Western blot confirmed this finding using isolated rat TCs. Next, rat TCs in culture were treated with LH in the presence or absence of HG, a highly specific SIK inhibitor. SIK inhibition enhanced the stimulatory effect of LH on Cyp17a1 mRNA expression. HG alone also increased Cyp17a1 expression to levels higher than those found in the presence of LH. Similarly, HG alone increased testosterone and potentiated LH stimulation of testosterone production. SIK inhibition also enhanced the stimulatory effect of LH on the expression of StAR and Cyp11a1. Concentration-response experiments for the SIK inhibitor in the presence or absence of LH show that SIK inhibition stimulates Cyp17a1 in a concentration-dependent manner from 0.1 to 1 µM. Of note, at 3 µM, HG was less effective in inducing Cyp17a1 than at 1 µM, suggesting that higher concentrations of HG may have alternative unknown effects. Activation of adenyl cyclase with forskolin or emulation of increased intracellular cAMP with dbcAMP stimulated Cyp17a1 an effect that was also enhanced by the inhibition of SIK. Since the main target of cAMP is PKA, we used lentivirus to express constitutively active PKA (caPKA). Overexpression of caPKA was sufficient to stimulate testosterone production, an effect that was significantly augmented by SIK inhibition, suggesting that SIKs regulate factors downstream of PKA. This evidence shows that TCs express SIKs and reveal novel roles for SIKs in the regulation of TC function and androgen production. This information could contribute to uncovering therapeutic targets to treat hyperandrogenic diseases such as PCOS. Presentation: Friday, June 16, 2023

A-056 Data Driven Approach to Ensure Accurate Total Testosterone Results in Consumer Initiated, Home-collected Capillary Samples

Abstract Background Home-collected direct access testing (DAT) has become increasingly attractive as telehealth utilization advances. With DAT, consumers initiate their lab order and have access to clinical consulting staff. Steroid hormone concentrations are uniquely positioned for DAT due to their inherent stability and non-acute indications. Total testosterone (TT) is used to screen for or monitor treatment of hypogonadism. Once diagnosed, testosterone is administered by intramuscular or subcutaneous injection or via transdermal patch or topical gel. TT in adult men is typically between 200 and 900 ng/dL. However, in our DAT lab we were encountering a significant percentage of samples with supraphysiological TT concentrations (&amp;gt;1500 ng/dL). The objective of this study was to design a quality assurance workflow to differentiate whether the supraphysiological results were accurate or erroneous. Methods TT was measured using the Roche Cobas e801 immunoassay; basic assay parameters were verified per general CAP guidelines (precision, accuracy, linearity, method comparison, interferences, carryover, dilution). Additional validation experiments were performed to verify that capillary plasma was an acceptable sample type (n = 30 paired capillary/venous samples) and to determine if extreme summer temperature fluctuations would influence stability (n = 46 participants; samples subjected to temperature cycling for 72 h before re-evaluation). Self-collected capillary samples received for clinical testing with a TT concentration &amp;gt;1500 ng/dL were run on a 1:5 dilution (extending the clinical reportable range to 7500 ng/dL) and the sample was reflexed to luteinizing hormone (LH) and follicle stimulating hormone (FSH). Reference intervals in adult men for LH and FSH are 1.7–8.6 mIU/mL and 1.4–13.0 mIU/mL, respectively. When available, clinical notes were reviewed for additional information on exogenous hormone usage. Results All general assay parameters were within acceptable metrics. TT concentrations between capillary and venous samples had an average absolute bias of −9.2 ng/dL or −3.8% (n = 30; range = &amp;lt;20–823 ng/dL; y = 0.954x + 1.915; R = 0.995). Baseline and post-summer temperature cycling TT concentrations had an average absolute bias of −8.1ng/dL or −3.4% (n = 46; range = &amp;lt;20–716 ng/dL; y = 0.934x + 7.728; R = 0.999). Samples (n = 506) with a TT concentration &amp;gt;1500 ng/dL were reflexed to TT dilution and LH/FSH. Most (n = 413; 82%) had undetectable (&amp;lt;0.3 mIU/mL) LH/FSH and a mean TT concentration of 3356 ng/dL (SD = 1972). For 18.6% (n = 77) of this subset, we had medication information; 68 were using injectable testosterone. Elevated TT was likely a true result caused by overuse of anabolic steroids. A smaller subset of samples (n = 21) had detectable LH/FSH with mean concentration/SD of 6.1/5.2 mIU/mL for LH, 5.3/5.4 mIU/mL for FSH, and TT &amp;gt;7500 ng/dL. Medication notes were available for 5 of these samples and indicated that the TT results were likely caused by topical contamination (false positive). A final subset (n = 40) had detectable LH/FSH and TT between 1500 and 7500 ng/dL. These samples could not be binned into simple categories and instead were sent to the lab director for review. Conclusion Self-collected capillary specimens are acceptable for TT measurements. A quality assurance reflex to LH/FSH can support or refute the validity of supraphysiological results in a consumer initiated/DAT population.

Effect of exercise on the hypothalamic–pituitary–gonadal axis in a rat model of Alzheimer’s disease

Hypothalamic–pituitary–gonadal (HPG) axis dysregulation was suggested to play a crucial role in Alzheimer’s disease (AD). This study investigated the effects of exercise on HPG hormones in an AD rat model, as a possible mechanism underlying the favorable effect of exercise on AD. Forty male Wistar albino rats 2–3 months old were subdivided randomly into two groups (n = 20 each): AD group (injected intraperitoneally with aluminum chloride (70 mg/kg/day) for 6 weeks) and Control group. Each group was subdivided into exercised or non-exercised group (n = 10 each). Exercised groups were subjected to a swimming protocol (60 min/day, 5 days/week, 4 weeks). Serum HPG hormones, hippocampal β-amyloid levels and Morris water-maze cognition were assessed. Results demonstrated higher levels of β-amyloid, gonadotropin releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) together with lower testosterone levels and cognitive impairment in the AD rats compared to controls. Β-amyloid levels negatively correlated with testosterone levels and positively correlated with GnRH, LH and FSH among the AD rats. Higher testosterone and lower GnRH, LH, FSH and β-amyloid levels, as well as cognitive improvement, were observed in the exercised compared to non-exercised AD rats, suggesting a modulatory role of exercise training on AD-associated HPG axis dysregulation.

Screening the possible effect of a phytofabricated nanoselenium-composite from Eruca sativa extract in reducing infertility in males

The antifertility effects of ketoconazole can be avoided or diminished by administering nano-selenium-based-antioxidant plant extract simultaneously or sequentially. Using selenium as nanoparticles (SeNPs) is one of the essential methods for enhancing its therapeutic effects and lowering toxicities. This study aimed to analyze the changes made to the parameters of androgens, such as testosterone and gonadotropin hormones: luteinizing hormone and follicle stimulating hormones together with sperm indexes after administration of antioxidant phytofabricated nanoselenium to mitigate oxidative damage brought on by ketoconazole. In brief, 1% weight-per-volume of the extract was loaded into a solution of 10 mM sodium selenite in various ratios on a magnetic stirrer (50 °C, PH 9) in the dark for 12 hours, left for 48 hours and then sent for characterization, which was performed using ultraviolet-visible spectroscopy (UV-vis spectra), Fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS). Then after the selection of the solution containing the optimal fabricated selenium nanoparticles it was administered to three groups out of seven groups of albino rats with eight animals in each one as follows: Gr. A negative control (no treatment), Gr. B oral ketoconazole 50 mg/kg for fourteen days, Gr. BC, BD, BE1, BE2 and BE3; each one received oral ketoconazole 50 mg/kg for fourteen days followed by: 200 mg/kg Eruca sativa (Gr. BC), 0.5 mg/kg oral sodium selenite (Gr. BD), 0.5 mg/kg/cm2 skin area local nanoselenium (Gr. BE1), 0.25 mg/kg oral nanoselenium (Gr. BE2) and 0.5 mg/kg oral nano selenium (Gr. BE3) respectively for 28 days. After this period, the animals were anesthetized, and plasma testosterone, luteinizing, and follicle stimulating hormones were assessed using Elisa Kit; after that, they were euthanized, and the epididymis of the right testis was carefully removed for evaluation of sperm indices (count, viability, abnormality, and motility). The reduction of selenium ions into PF-SeNPs induced by Eruca sativa extracts at a ratio of (1:2) (Na2SeO3: Eruca sativa) solution was confirmed by the gradual conversion of colour from dark brown to light yellow and then to reddish-orange after the addition of acidic sodium selenite solution and reacting for 12 h. The final reddish-orange colour is the most significant property of nanoparticles. In UV-vis spectroscopy, a strong absorption peak appeared between 268–964 nm with maxima at 268 nm, confirming the formation of nanoselenium. The optimal phytofabricated nanoselenium particles were obtained with a spherical shape, highly stable, and the smallest in size (39.4 nm in diameter) as proved by DLS with Poly Dispersity Index of 0.242 and zeta potential value of –56.57 mV. In the current study, testicles were damaged by administering ketoconazole at a dose of 50 mg/kg/day orally for 14 days. This testicular damage was linked to significant reductions in testosterone levels, elevated levels of LH and FSH, and significant decreases in sperm count, motility, and viability, which in turn affected spermatogenesis. Concurrently, the administration of Eruca sativa extract, sodium selenite and nanoselenium solution (in different doses and routes) following ketoconazole was shown to significantly improve biochemical parameters. These improvements included an increase in testosterone levels with little to no impact on LH and FSH levels as well as improved sperm indices. Additionally, the oral nanoselenium groups in 0.25 and 0.50 mg/kg produced the best outcomes with only minor differences between them. In conclusion, the antioxidant effects of the phytofabricated nanoselenium-based Eruca sativa leaf extract considerably improved testicular tissues.

The role of GnRH in Tibetan male sheep and goat reproduction.

The hypothalamic-pituitary-gonadal (HPG) axis connects the hypothalamus, pituitary gland, and gonads. The regulation of reproductive processes includes integrating various factors from structural functions and environmental conditions in the HPG axis, with the outcome indication of these processes being the pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. These factors include feed consumption and nutritional condition, sex steroids, season/photoperiod, pheromones, age, and stress. GnRH pulsatile secretion affects the pattern of gonadotropin secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which then regulates both endocrine function and gamete maturation in the gonads. This regulates gonadotropins and testosterone (T) production. There is evidence that in males, GnRH participates in a variety of host behavioural and physiological processes such as the release of reproductive hormones, progression of spermatogenesis and sperm function, aggressive behaviour, and physiological metabolism. GnRH activates receptors expressed on Leydig cells and Sertoli cells, respectively to stimulate T secretion and spermatogenesis in the testis. Photoperiod affects the reproductive system of the hypothalamic-pituitary axis via rhythmic diurnal melatonin secretion. Increased release of melatonin promotes sexual activity, GnRH production, LH stimulation, and T production. This induces testicular functions, spermatogenesis, and puberty. GnRH reduces the release of LH by the pituitary through the cascade effect and decreases plasma concentration of T. Gut microbiota maintain sex steroid homeostasis and may induce reduction in reproduction productivity. Recently, findings of kisspeptin-neurokinin-dynorphin neuronal network in the brain have resulted in fast advances in how GnRH secretion is controlled. Emerging studies have also indicated that other neuropeptide analogues could be used in control reproduction procedures in various goat and sheep breeds. The Tibetan male sheep and goats reproduce on a seasonal basis and have high reproductive performance. This is a review for the role of GnRH in Tibetan male sheep and goats reproduction. This is intended to enhance reproductive knowledge for understanding the key roles of GnRH relating to male reproductive efficiency of Tibetan sheep or goats.

Methionine metabolism and endocrine function of the pituitary gland in patients with suprasellar germinoma.

The aim of this study was to investigate the association between methionine (MET) metabolism and endocrine function of the pituitary gland in patients with suprasellar region tumor. Twenty patients with intracranial germinoma were included in this study. Initial staging and all surveillance MET PET/CT scans and comparable serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid stimulating hormone (TSH) were analyzed. The patients were divided into two groups according to tumor location, with tumors in the suprasellar region (condition) or not (control). MET uptake of the pituitary gland (i.e., SUVR [standardized uptake value ratio]) and levels of FSH, LH, TSH were compared in the condition and control groups and in the before and after treatment phases of each group. The SUVR in the control group was like that found in normal pituitary glands in previous studies, whereas the SUVR of the untreated condition group was high and that of treated condition group was low with significance compared to the control group. Serum levels of pituitary hormones in before and after treatment condition groups were significantly lower than those in the control group. The FSH and LH levels of curatively treated patients in the control group were positively correlated with SUVR with respective ß values of 3.71 and 0.98 (p < .001). The TSH level of the treated condition group was negatively correlated with SUVR (ß = -1.02, p < .001). This study is the first known investigation to examine the association between MET metabolism and endocrine function of the pituitary gland, and it confirmed that MET metabolism reflects endocrine function. A future study validating the result of correlation analysis is warranted.

Co-administration of thymol and sulfoxaflor impedes the expression of reproductive toxicity in male rats

This study investigated the capability of a co-delivery system of thymol (THY) and sulfoxaflor that can serve to minimize the development of epididymal and testicular injury arise from SFX exposures alone. Forty-eight adult male rats were orally treated by gavage for 28 consecutive days. The rats were divided into six groups comprising control, THY alone (30 mg/kg), low SFX alone (79.4 mg/kg), high SFX alone (205 mg/kg) and co-exposure groups. After euthanasia, the rats epididymal and testicular damage and antioxidant status markers, myeloperoxidase (MPO) activity, levels of nitric oxide, total antioxidant capacity (TAC), total oxidative stress (TOS) and lipid peroxidation (LPO) were analyzed. Levels of tumor necrosis factor alpha (TNF-α), interleukin-1 b (IL-1β) and caspase-3 activity were assessed using ELISA kits. The results revealed that SFX exposure caused a significant (p < 0.05) decrease in the body weight, sperm functional parameters, serum testosterone level with widespread histological abnormalities in a dose-dependent manner. Increased relative organ weights, serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were observed in low SFX-treated rats. Similarly, the epididymal and testicular myeloperoxidase activity, malondialdehyde (MDA), reactive oxygen species (RONS), tumor necrosis-α, interleukin-1β levels and caspase-3 activity were significant (p < 0.05) increased and a significant (p < 0.05) reduction in antioxidant enzyme activities and reduced glutathione (GSH) were revealed in SFX-treated rats. However, co-treatment of THY with SFX prevented SFX-induced epididymal and testicular toxicities. Thus, thymol protected against potential epididymis and testes alterations elicited by oxido-inflammatory mediators and up regulated antioxidant status.

Short term effects of intraarticular triamcinolone acetonide injection on serum testosterone, luteinizing hormone, and follicle stimulating hormone levels in male veterans: A prospective pilot study.

Despite the common practice of intraarticular corticosteroid injections (ICSIs) for peripheral joint disease, little is known about their systemic effects on the hypothalamic-pituitary-gonadal axis. To assess the short-term effects of ICSIs on serum testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels together with changes in Shoulder Pain and Disability Index (SPADI) scores in a veteran population. Prospective pilot study. Outpatient musculoskeletal clinic. Thirty male veterans, median age 50 (range 30-69) years. Ultrasound-guided glenohumeral joint injection using 3 mL of 1% lidocaine HCl and 1 mL of 40 mg triamcinolone acetonide (Kenalog). Serum T, FSH, and LH levels, Quantitative Androgen Deficiency in the Aging Male (qADAM), and SPADI questionnaires at baseline, 1, and 4 week(s) post procedure. At 1 week post injection, serum T levels decreased by 56.8 ng/dL (95% confidence interval (CI): 91.8, 21.7, p = .002) compared with baseline. Between 1 and 4 weeks post injection, serum T levels increased by 63.9 ng/dL (95% CI: 26.5, 101.2, p = .001), recovering to near baseline levels. SPADI scores were reduced at 1 week (-18.3, 95% CI: -24.4, -12.1, p < .001) and 4 weeks (-14.5, 95% CI -21.1, -7.9, p < .001). A single ICSI can temporarily suppress the male gonadal axis. Future studies are needed to evaluate for long-term effects of multiple injections at a single setting and/or higher corticosteroid doses on male reproductive axis function.

Serum organophosphate flame retardants and plasticizers in Chinese females of childbearing age: Association with serum reproductive and thyroid hormones

Organophosphate flame retardants (OPFRs) are extensively used as flame retardants and plasticizers, but their endocrine disrupting potentials have raised concerns. However, the impacts of OPFR exposures on reproductive and thyroid hormones in females remains unclear. In this study, serum concentrations of OPFRs were investigated, and levels of reproductive and thyroid hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, anti-Müllerian hormone, prolactin (PRL), testosterone (T), and thyroid stimulating hormone, were analyzed in childbearing-age females undergoing in-vitro fertilization treatment from Tianjin, a coastal city in China (n = 319). Tris (2-chloroethyl) phosphate (TCEP) was the predominant OPFR, with a median concentration of 0.33 ng/mL and a detection frequency of 96.6%. In the whole population, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-chloroisopropyl) phosphate (TCIPP) were positively associated with T (p < 0.05), while triethyl phosphate (TEP) was negatively associated with LH (p < 0.05) and LH/FSH (p < 0.01). Particularly, TCIPP was negatively associated with PRL in the younger subgroup (age≤30, p < 0.05). Moreover, TCIPP was negatively associated with diagnostic antral follicle counting (AFC) in the mediation analysis by a dominating direct effect (p < 0.01). In conclusion, serum levels of OPFRs were significantly associated with reproductive and thyroid hormone levels and a risk of decreased ovarian reserve in childbearing-age females, with age and body mass index being significant influencing factors.

#4184 MALE CHRONIC KIDNEY DISEASE IS A STATE OF PREMATURE TESTICULAR AGING

Abstract Background and Aims Sex steroid levels have been reported to be decreased in male patients with chronic kidney disease (CKD), parallel to the severity of the kidney dysfunction. These studies, at large, used immuno-assays, a method that is inferior to gold standard chromatography measurements and, in addition, failed to give insights into the underlying pathophysiology as they lacked data on gonadotropin levels. The aim of this study was to comprehensively map the gonadal status in male CKD patients not yet on dialysis and age- and BMI-matched controls, using gold standard techniques. Method We performed a case-control study in 120 male CKD patients (age 65.0 y, BMI 26.8 kg/m2), matched (1:1) with non-CKD controls for age and BMI. We divided CKD patients into 3 categories based on KDIGO classification: CKD 1–2 (n = 24), CKD 3 (n = 42) and CKD 4–5 (n = 54). We measured total testosterone (T) and estradiol (E2) using liquid chromatography tandem mass-spectrometry. Sex hormone binding globulin (SHBG), prolactin, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured on the Roche Cobas 8000 platform. Free T levels were calculated via Vermeulen formula. Inhibin B (a readout for testicular Sertoli cell function) was measured by ELISA. Results CKD patients showed lower total T (426.0 ng/dL [297.5-516.5] vs. 541.0 ng/dL [452.0-647.8]; p&amp;lt;0.0001) and free T levels (7.4 ng/dL ±3.2 vs. 9.4 ng/dL +/-2.2; p&amp;lt;0.0001) as compared to non-CKD counterparts. SHBG and E2 levels, conversely, were comparable in cases and controls. Inhibin B levels were lower in CKD patients as well (112.7 pg/mL [38.1-189.0] vs. 181.1 [122.2-236.4]; p&amp;lt;0.0001). LH and FSH levels were higher in CKD patients (9.1 IU/L [5.4-16.2] vs. 5.4 IU/L [3.6-8.1]; p&amp;lt;0.0001 and 7.8 IU/L [5.0-20.2] vs. 5.6 IU/L [4.0-9.7]; p&amp;lt;0.0001 respectively). Consequently, the T/LH ratio and inhibin B/FSH ratio, respectively reflecting Leydig and Sertoli cell function, were markedly depressed in CKD (1.8 nmol/IU [0.7-3.0] vs. 4.0 nmol/IU [2.4-5.2]; p&amp;lt;0.0001 and 14.4 ng/IU [1.2-33.6] vs. 32.2 ng/IU [32.2 [16.3-56.7]; p&amp;lt;0.0001). In the CKD cohort, regression analysis identified eGFR and age as independent determinants of T/LH ratio (R2 0.29). According to the T/LH ratio a male CKD patient of 45y old has a testicular age of an 81y old control. Conclusion Male patients with CKD not yet on dialysis show low total and free T levels, confirming CKD as a risk factor for male hypogonadism. The low T/LH and inhibin B/FSH ratio point to testicular failure as the underlying pathophysiological mechanism.