Influence of energy availability on metabolic hormonal profiles in east African female and male distance runners.

BACKGROUND: Energy availability (EA) and relative energy deficiency in sport (RED-S) are understudied in East African endurance athletes, both females (F) and males (M). This study assessed the metabolic hormonal profiles of such athletes relative to their EA status. METHODS: Forty athletes (F=16, M=24) had their EA status, training, maximal oxygen uptake, and resting blood samples assessed using standard research practices. Subjects were stratified into two groups, high EA (HiEA) and low EA (LoEA) based on combined median value. RESULTS: Cortisol (P=0.034) and insulin (P=0.044) were significantly elevated in the LoEA group, while growth hormone (P=0.045) was significantly suppressed; and, prolactin (P=0.078) trended towards suppression, respectively compared to the HiEA group. All other hormonal comparison were non-significant. CONCLUSIONS: Metabolic hormonal profiles of female and male African distance runners are affected by their EA status. Aspects of these alterations agree in part with published findings based upon White populations, although some differences exist and need further investigation.

Unveiling an indole alkaloid diketopiperazine biosynthetic pathway that features a unique stereoisomerase and multifunctional methyltransferase.

The 2,5-diketopiperazines are a prominent class of bioactive molecules. The nocardioazines are actinomycete natural products that feature a pyrroloindoline diketopiperazine scaffold composed of two D-tryptophan residues functionalized by N- and C-methylation, prenylation, and diannulation. Here we identify and characterize the nocardioazine B biosynthetic pathway from marine Nocardiopsis sp. CMB-M0232 by using heterologous biotransformations, in vitro biochemical assays, and macromolecular modeling. Assembly of the cyclo-L-Trp-L-Trp diketopiperazine precursor is catalyzed by a cyclodipeptide synthase. A separate genomic locus encodes tailoring of this precursor and includes an aspartate/glutamate racemase homolog as an unusual D/L isomerase acting upon diketopiperazine substrates, a phytoene synthase-like prenyltransferase as the catalyst of indole alkaloid diketopiperazine prenylation, and a rare dual function methyltransferase as the catalyst of both N- and C-methylation as the final steps of nocardioazine B biosynthesis. The biosynthetic paradigms revealed herein showcase Nature's molecular ingenuity and lay the foundation for diketopiperazine diversification via biocatalytic approaches.

Marathon Running and Sexual Libido in Adult Men: Exercise Training and Racing Effects.

We examined whether endurance training for a standard marathon (42.2 km) had a greater influence on male libido than more generalized endurance exercise training. We surveyed adult men (>1000) who regularly engaged in endurance running to evaluate exercise training histories-patterns and libido characteristics. Our participants were primarily recruited from North America and Europe. Results indicate men conducting marathon training had lower libido scores (p<0.05; ~20%, d=0.44) than those not doing such specific training. Factors most related to libido were: 1) the number of years of training, and 2) the proportion of high-intensity effort conducted in training (inverse relationships); regardless of whether marathon training was performed or not. Our survey approach did not allow us to determine the cause of the reduced libido, but we speculate it could relate to: 1) chronic physical fatigue from high volumes of exercise training, 2) behavioral accommodations in energy expenditure, or else 'Relative Energy Deficiency in Sport' (RED-S) syndrome, and/or 3) endocrinological adaptations as a result of the exercise training (i.e., low testosterone). From a practical perspective, we recommend couples attempting conception should inform their healthcare providers of the male partner's exercise habits concerning endurance running as this may be a factor relative to potential infertility.

Biomimetic Total Synthesis of (+)-Nocardioazine B and Analogs.

Nocardioazines A and B are prenylated, bioactive pyrroloindoline natural products, isolated from Nocardiopsis, with a desymmetrized cyclo-d-Trp-d-Trp DKP core. Based on our deeper biosynthetic understanding, a biomimetic total synthesis of (+)-nocardioazine B is accomplished in merely seven steps and 23.2% overall yield. This pathway accesses regio- and stereoselectively C3-isoprenylated analogs of (+)-nocardioazine B, using the same number of steps and in similar efficiency. The successful strategy mandated that the biomimetic C3-prenylation step be executed early. The use of an unprotected carboxylic acid of Trp led to high diastereoselectivity toward formation of key intermediates exo-12a, exo-12b, and exo-12c (>19:1). Evidence shows that N1-methylation causes the prenylation reaction to bifurcate away to result in a C2-normal-prenylated isomer. Nocardioazine A, possessing an isoprenoidal-epoxide bridge, inhibits P-glycoprotein (P-gp)-mediated membrane efflux, in multidrug-resistant mammalian colon cancer cells. As several P-gp inhibitors have failed due to their toxicity effects, endogenous amino-acid-derived noncytotoxic inhibitors (from the nocardioazine core) are worthy leads toward a rejuvenated strategy against resistant carcinomas. This total synthesis provides direct access to Trp-derived isoprenylated DKP natural products and their derivatives.

Prevalence of Triad-RED-S symptoms in high-level Kenyan male and female distance runners and corresponding control groups.

PURPOSE: This study examined and compared select Triad-RED-S components/risk factors in high-level Kenyan male and female distance runners to corresponding control groups; focusing on examining energy intake (EI), bone indices, and hormonal markers. METHODS: A cross-sectional, observational design was used in which Kenyan male and female (n = 30 and n = 26, respectively) middle- and long-distance runners and corresponding male and female control groups (n = 29 and n = 29, respectively) were examined. The participant's bone mineral density (BMD) at the lumbar spine, right femur, and total body were measured using a dual-energy X-ray absorptiometry analysis. Complete blood counts (CBC) were done on the whole blood specimens and hormonal measurements were performed on plasma specimens. In addition, athletes completed metabolic testing to determine maximal oxygen uptakes and 7-day dietary diaries. RESULTS: Overall daily EI across runners and controls within each sex were low, but not significantly different (p > 0.05). Prevalence of low BMD values (Z score < - 2.0) was comparable across groups in each sex (p > 0.05). CBC measures suggested that both runners and controls were healthy. Finally, slight hormonal differences between runners and their respective controls existed (p < 0.05), but were not clinically meaningful or observed in typical Triad-RED-S-related parameters. CONCLUSION: High-level Kenyan male and female runners had low daily EI, but no tendency toward a higher prevalence of low BMD, or Triad-RED-S-related hormonal abnormalities. The occurrence of low EI was not a major risk factor in our athletes; this calls into question whether the current criteria for Triad-RED-S are entirely applicable for athletes of African ethnicity.

Energy Availability and RED-S Risk Factors in Competitive, Non-elite Male Endurance Athletes.

Relative Energy Deficiency in Sport (RED-S) is predicated on the assumption that low energy availability (EA) induces deficiencies-dysfunction in multiple physiologic systems. However, research on RED-S and EA in male athletes is limited in comparison to women. The aim of this study is to investigate EA and the risk factors for RED-S, and their potential associations in non-elite male endurance athletes. Laboratory assessments for resting metabolic rate (RMR), bone mineral density (BMD), blood hormonal biomarkers and maximal aerobic capacity were conducted on 60 competitive, recreationally trained male endurance athletes (age=43.4±11.6 years [mean±SD], training=10.9±2.7 h/wk, 7.1±8.8 years). Participants provided 7-days of training logs and 4-days of diet records. Diet and training records were used to calculate EA. Correlations were used to examine associations between EA and RMR, BMD, stress fractures and reproductive, metabolic and bone biomarkers. Mean EA was 28.7±13.4 kcal/kg fat free mass (FFM), which categorized our sample as low EA (based upon published criterion, < 30 kcal/kg FFM) and at a high risk for RED-S. Hormonal and bone biomarkers were in normal clinical ranges, even though EA was low. The only interesting significant association was EA being negatively associated with total body BMD (r = -0.360, P =0.005), opposite of expectations. On average our subjects displayed a state of low EA based upon the criterion which has been primarily developed from female-based research. Nonetheless, our participants displayed no major hormonal or bone health disturbances found in athletes diagnosed with RED-S. A value of < 30 kcal/kg FFM to diagnose low EA may not be appropriate for non-elite endurance trained men.

Bioinspired Brønsted Acid-Promoted Regioselective Tryptophan Isoprenylations.

Tryptophan-containing isoprenoid indole alkaloid natural products are well known for their intricate structural architectures and significant biological activities. Nature employs dimethylallyl tryptophan synthases (DMATSs) or aromatic indole prenyltransferases (iPTs) to catalyze regio- and stereoselective prenylation of l-Trp. Regioselective synthetic routes that isoprenylate cyclo-Trp-Trp in a 2,5-diketopiperazine (DKP) core, in a desymmetrizing manner, are nonexistent and are highly desirable. Herein, we present an elaborate report on Brønsted acid-promoted regioselective tryptophan isoprenylation strategy, applicable to both the monomeric amino acid and its dimeric l-Trp DKP. This report outlines a method that regio- and stereoselectively increases sp3 centers of a privileged bioactive core. We report on conditions involving screening of Brønsted acids, their conjugate base as salt, solvent, temperature, and various substrates with diverse side chains. Furthermore, we extensively delineate effects on regio- and stereoselection of isoprenylation and their stereochemical confirmation via NMR experiments. Regioselectively, the C3-position undergoes normal-isoprenylation or benzylation and forms exo-ring-fused pyrroloindolines selectively. Through appropriate prenyl group migrations, we report access to the bioactive tryprostatin alkaloids, and by C3-normal-farnesylation, we access anticancer drimentines as direct targets of this method. The optimized strategy affords iso-tryprostatin B-type products and predrimentine C with 58 and 55% yields, respectively. The current work has several similarities to biosynthesis, such as-reactions can be performed on unprotected substrates, conditions that enable Brønsted acid promotion, and they are easy to perform under ambient conditions, without the need for stoichiometric levels of any transition metal or expensive ligands.

Shorter Ground Contact Time and Better Running Economy: Evidence From Female Kenyan Runners.

ABSTRACT: Mooses, M, Haile, DW, Ojiambo, R, Sang, M, Mooses, K, Lane, AR, and Hackney, AC. Shorter ground contact time and better running economy: evidence from female Kenyan runners. J Strength Cond Res 35(2): 481-486, 2021-Previously, it has been concluded that the improvement in running economy (RE) might be considered as a key to the continued improvement in performance when no further increase in V̇o2max is observed. To date, RE has been extensively studied among male East African distance runners. By contrast, there is a paucity of data on the RE of female East African runners. A total of 10 female Kenyan runners performed 3 × 1,600-m steady-state run trials on a flat outdoor clay track (400-m lap) at the intensities that corresponded to their everyday training intensities for easy, moderate, and fast running. Running economy together with gait characteristics was determined. Subjects showed moderate to very good RE at the first (202 ± 26 ml·kg-1·km-1) and second (188 ± 12 ml·kg-1·km-1) run trials, respectively. Correlation analysis revealed significant relationship between ground contact time (GCT) and RE at the second run (r = 0.782; p = 0.022), which represented the intensity of anaerobic threshold. This study is the first to report the RE and gait characteristics of East African female athletes measured under everyday training settings. We provided the evidence that GCT is associated with the superior RE of the female Kenyan runners.

A Virtual Screening Platform Identifies Chloroethylagelastatin A as a Potential Ribosomal Inhibitor.

Chloroethylagelastatin A (CEAA) is an analogue of agelastatin A (AA), a natural alkaloid derived from a marine sponge. It is under development for therapeutic use against brain tumors as it has excellent central nervous system (CNS) penetration and pre-clinical therapeutic activity against brain tumors. Recently, AA was shown to inhibit protein synthesis by binding to the ribosomal A-site. In this study, we developed a novel virtual screening platform to perform a comprehensive screening of various AA analogues showing that AA analogues with proven therapeutic activity including CEAA have significant ribosomal binding capacity whereas therapeutically inactive analogues show poor ribosomal binding and revealing structural fingerprint features essential for drug-ribosome interactions. In particular, CEAA was found to have greater ribosomal binding capacity than AA. Biological tests showed that CEAA binds the ribosome and contributes to protein synthesis inhibition. Our findings suggest that CEAA may possess ribosomal inhibitor activity and that our virtual screening platform may be a useful tool in discovery and development of novel ribosomal inhibitors.

Auranofin improves overall survival when combined with standard of care in a pilot study involving dogs with osteosarcoma.

Osteosarcoma is the most common paediatric primary bone malignancy. The major cause of death in osteosarcoma is drug-resistant pulmonary metastasis. Previous studies have shown that thioredoxin reductase 2 is a driver of metastasis in osteosarcoma and can be inhibited by auranofin (AF). Moreover, studies have shown that AF significantly reduces pulmonary metastases in xenotransplant models. Here, we describe a phase I/II study of AF in canine osteosarcoma, a well-recognized spontaneous model of human osteosarcoma. We performed a single-arm multicentre pilot study of AF in combination with standard of care (SOC) (amputation + carboplatin). We recruited 40 dogs to the trial and used a historical SOC-only control group (n = 26). Dogs >15 kg received 9 mg AF q3d PO and dogs <15 kg received 6 mg q3d. Follow-up occurred over at least a 3-year period. Auranofin plus SOC improved overall survival (OS) (P = .036) in all dogs treated. The improved outcome was attributable entirely to improved OS in male dogs (P = .009). At the time of writing, 10 dogs (25%) survive without measurable disease in the treatment group with survival times ranging between 806 and 1525 days. Our study shows that AF improves OS in male dogs when combined with SOC. Our findings have translational relevance for the management of canine and human osteosarcoma. Our data justify a larger multicentre phase 2 trial in dogs and a phase I/II trial in human patients with refractory disease at the time of initial surgery.

Prevalence of Low Energy Availability in Competitively Trained Male Endurance Athletes.

Background and Objectives: Relative energy deficiency in sport (RED-S) has been introduced as a broad-spectrum syndrome leading to possible dysfunction in numerous physiological systems, driven primarily by low energy availability (EA). Research in females has identified specific EA cut-points indicative of risk level for developing physiological and performance disturbances. Cut-points in males have yet to be evaluated. This study examined the prevalence of low EA in competitive (non-elite), recreationally trained (CRT) male endurance athletes. Materials and Methods: Subjects were 108 CRT (38.6 ± 13.8 y; 12.2 ± 5.4 h/wk training) male endurance athletes (runners, cyclists, triathletes) who completed a descriptive survey online via Qualtrics® and returned 3 day diet and exercise training records. EA was calculated from returned surveys and training records. Resting metabolic rate (RMR) and lean body mass (LBM) were estimated from self-reported survey data. Prevalence of risk group was categorized based on the female cut-points: at risk (AR) ≤30 kcal/kg LBM, moderate risk (MR) = 30-45 kcal/kg LBM, or no risk (NR) ≥45 kcal/kg LBM. Results: In this sample, 47.2% (n = 51) were classified as AR, 33.3% (n = 36) as MR, and 19.4% (n = 21) as NR for low EA. Cyclists had lower EA (26.9 ± 17.4 kcal/kg LBM, n = 45) than runners (34.6 ± 13.3 kcal/kg LBM, n = 55, p = 0.016) and all other sport categories (39.5 ± 19.1 kcal/kg LBM, n = 8, p = 0.037). Conclusions: The findings indicate this sample had a high prevalence of risk for low EA, at 47.2%. Only 19.4% of participants were at no risk, meaning ~80% of participants were at some degree of risk of experiencing low EA. Cyclists were at greater risk in this cohort of low EA, although why this occurred was unclear and is in need of further investigation. Future research should address whether the current female cut-points for low EA are appropriate for use in male populations.

Disfunción reproductiva por entrenamiento físico: el "hipogonadismo masculino producto del ejercicio" / Reproductive Dysfunction from Exercise Training: The "Exercise-Hypogonadal Male Condition"

El objetivo de esta breve revisión es describir cómo el entrenamiento físico en hombres puede provocar cambios en el sistema reproductivo similares a los observados en mujeres que desarrollan amenorrea atlética o manifiestan la tríada de la mujer atleta. Hombres expuestos sistemáticamente a entrenamientos para deportes de resistencia exhiben concentraciones de testosterona libre y basal reducidas, pero sin manifestar un aumento simultáneo de hormona luteinizante. Esta condición se denomina "hipogonadismo masculino producto del ejercicio" (EHMC, por sus siglas en inglés). Ambos estados están asociados a una disfunción en el eje hipotalámico-hipofisario-gonadal. En las mujeres, la alteración del eje está vinculada a un estado de baja disponibilidad energética (BDE); en los hombres, la investigación relacionada con la BDE está en curso. El mecanismo fisiológico exacto que induce la reducción de testosterona en estos hombres aún no está claro, pero se postula que es una disfunción dentro del eje regulador hipotalámico-hipofisario-gonadal. Existe la posibilidad de que las bajas concentraciones de testosterona de los hombres con EHMC sean disruptivas y perjudiciales para algunos procesos fisiológicos anabólico-androgénicos dependientes de testosterona. Los hallazgos, aunque limitados, sugieren que en algunos casos pueden existir problemas de espermatogénesis; por lo tanto, el riesgo de infertilidad en tales hombres es una preocupación crucial. La evidencia actual sugiere que el EHMC se limita a hombres que han estado involucrados en entrenamiento de resistencia de manera persistente y durante tiempo prolongado, por lo que el EHMC no es una condición prevalente. De todos modos, es fundamental que médicos endocrinólogos y especialistas en fertilidad estén atentos a la existencia del EHMC como potencial problema - y diagnostico - que pueden padecer sus pacientes deportistas varones

The objective of this short review is to discuss how exercise training in men can result in changes in the reproductive system similar to those observed in women who develop athletic amenorrhea or suffer the Female Athlete Triad. Men chronically exposed to training for endurance sports exhibit persistently reduced basal free and total testosterone concentrations without concurrent luteinizing hormone elevations. These men are deemed to have the "Exercise-Hypogonadal Male Condition" (EHMC). Broadly, dysfunction in the hypothalamic-pituitary-gonadal regulatory axis is associated with either of these states. In women this effect on the axis is linked to the existence of a low energy availability (LEA) state, research in men relative to LEA is ongoing. The exact physiological mechanism inducing the reduction of testosterone in these men is currently unclear but is postulated to be a dysfunction within the hypothalamic-pituitary-gonadal regulatory axis. The potential exists for the reduced testosterone concentrations within EHMC men to be disruptive and detrimental to some anabolic-androgenic testosterone-dependent physiological processes. Findings, while limited, suggest spermatogenesis problems may exist in some cases; thus, infertility risk in such men is a critical concern. Present evidence suggests the EHMC condition is limited to men who have been persistently involved in chronic endurance exercise training for an extended period of time, and thus is not a highly prevalent occurrence. Nevertheless, it is critical that endocrinologist and fertility clinicians become more aware of the existence of EHMC as a potential problem-diagnosis in their male patients who exercise

An Isotopic Ratio Outlier Analysis Approach for Global Metabolomics of Biosynthetically Talented Actinomycetes.

Actinomycetes are powerhouses of natural product biosynthesis. Full realization of this biosynthetic potential requires approaches for recognizing novel metabolites and determining mediators of metabolite production. Herein, we develop an isotopic ratio outlier analysis (IROA) ultra-high performance liquid chromatography-mass spectrometry (UHPLC/MS) global metabolomics strategy for actinomycetes that facilitates recognition of novel metabolites and evaluation of production mediators. We demonstrate this approach by determining impacts of the iron chelator 2,2'-bipyridyl on the Nocardiopsis dassonvillei metabolome. Experimental and control cultures produced metabolites with isotopic carbon signatures that were distinct from corresponding "standard" culture metabolites, which were used as internal standards for LC/MS. This provided an isotopic MS peak pair for each metabolite, which revealed the number of carbon atoms and relative concentrations of metabolites and distinguished biosynthetic products from artifacts. Principal component analysis (PCA) and random forest (RF) differentiated bipyridyl-treated samples from controls. RF mean decrease accuracy (MDA) values supported perturbation of metabolites from multiple amino acid pathways and novel natural products. Evaluation of bipyridyl impacts on the nocazine/XR334 diketopiperazine (DKP) pathway revealed upregulation of amino acid precursors and downregulation of late stage intermediates and products. These results establish IROA as a tool in the actinomycete natural product chemistry arsenal and support broad metabolic consequences of bipyridyl.

Correction: The expanding spectrum of diketopiperazine natural product biosynthetic pathways containing cyclodipeptide synthases.

Correction for 'The expanding spectrum of diketopiperazine natural product biosynthetic pathways containing cyclodipeptide synthases' by Paul Borgman et al., Org. Biomol. Chem., 2019, DOI: 10.1039/c8ob03063d.

Body Mass Index and Type 2 Collagen Turnover in Individuals After Anterior Cruciate Ligament Reconstruction.

CONTEXT: Individuals with an anterior cruciate ligament reconstruction (ACLR) are at an increased risk of developing posttraumatic osteoarthritis. How osteoarthritis risk factors, such as increased body mass index (BMI), may influence early changes in joint tissue metabolism is unknown. OBJECTIVE: To determine the association between BMI and type 2 cartilage turnover in individuals with an ACLR. DESIGN: Cross-sectional study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Forty-five individuals (31 women, 14 men) with unilateral ACLR at least 6 months earlier who were cleared for unrestricted physical activity. MAIN OUTCOME MEASURE(S): Body mass index (kg/m2) and type 2 collagen turnover were the primary outcomes. Body mass index was calculated from objectively measured height and mass. Serum was obtained to measure type 2 collagen turnover, quantified as the ratio of degradation (collagen type 2 cleavage product [C2C]) to synthesis (collagen type 2 C-propeptide [CP2]; C2C : CP2). Covariate measures were physical activity level before ACLR (Tegner score) and current level of disability (International Knee Documentation Committee Index score). Associations of primary outcomes were analyzed for the group as a whole and then separately for males and females. RESULTS: Overall, greater BMI was associated with greater C2C : CP2 (r = 0.32, P = .030). After controlling for covariates (Tegner and International Knee Documentation Committee Index scores), we identified a similar association between BMI and C2C : CP2 (partial r = 0.42, P = .009). Among women, greater BMI was associated with greater C2C : CP2 before (r = 0.47, P = .008) and after (partial r = 0.50, P = .008) controlling for covariates. No such association occurred in men. CONCLUSIONS: Greater BMI may influence greater type 2 collagen turnover in those with ACLR. Individuals, especially women, who maintain or reduce BMI may be less likely to demonstrate greater type 2 collagen turnover ratios after ACLR.

The expanding spectrum of diketopiperazine natural product biosynthetic pathways containing cyclodipeptide synthases.

Microorganisms are remarkable chemists, with enzymes as their tools for executing multi-step syntheses to yield myriad natural products. Microbial synthetic aptitudes are illustrated by the structurally diverse 2,5-diketopiperazine (DKP) family of bioactive nonribosomal peptide natural products. Nonribosomal peptide synthetases (NRPSs) have long been recognized as catalysts for formation of DKP scaffolds from two amino acid substrates. Cyclodipeptide synthases (CDPSs) are more recently recognized catalysts of DKP assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. CDPS-encoding genes are typically found in genomic neighbourhoods with genes encoding additional biosynthetic enzymes. These include oxidoreductases, cytochrome P450s, prenyltransferases, methyltransferases, and cyclases, which equip the DKP scaffold with groups that diversify chemical structures and confer biological activity. These tailoring enzymes have been characterized from nine CDPS-containing biosynthetic pathways to date, including four during the last year. In this review, we highlight these nine DKP pathways, emphasizing recently characterized tailoring reactions and connecting new developments to earlier findings. Featured pathways encompass a broad spectrum of chemistry, including the formation of challenging C-C and C-O bonds, regioselective methylation, a unique indole alkaloid DKP prenylation strategy, and unprecedented peptide-nucleobase bond formation. These CDPS-containing pathways also provide intriguing models of metabolic pathway evolution across related and divergent microorganisms, and open doors to synthetic biology approaches for generation of DKP combinatorial libraries. Further, bioinformatics analyses support that much unique genetically encoded DKP tailoring potential remains unexplored, suggesting opportunities for further expansion of Nature's biosynthetic spectrum. Together, recent studies of DKP pathways demonstrate the chemical ingenuity of microorganisms, highlight the wealth of unique enzymology provided by bacterial biosynthetic pathways, and suggest an abundance of untapped biosynthetic potential for future exploration.

Regenerative Failure Following Rat Neonatal Chorda Tympani Transection is Associated with Geniculate Ganglion Cell Loss and Terminal Field Plasticity in the Nucleus of the Solitary Tract.

Neural insult during development results in recovery outcomes that vary dependent upon the system under investigation. Nerve regeneration does not occur if the rat gustatory chorda tympani nerve is sectioned (CTX) during neonatal (≤P10) development. It is unclear how chorda tympani soma and terminal fields are affected after neonatal CTX. The current study determined the impact of neonatal CTX on chorda tympani neurons and brainstem gustatory terminal fields. To assess terminal field volume in the nucleus of the solitary tract (NTS), rats received CTX at P5 or P10 followed by chorda tympani label, or glossopharyngeal (GL) and greater superficial petrosal (GSP) label as adults. In another group of animals, terminal field volumes and numbers of chorda tympani neurons in the geniculate ganglion (GG) were determined by labeling the chorda tympani with DiI at the time of CTX in neonatal (P5) and adult (P50) rats. There was a greater loss of chorda tympani neurons following P5 CTX compared to adult denervation. Chorda tympani terminal field volume was dramatically reduced 50 days after P5 or P10 CTX. Lack of nerve regeneration after neonatal CTX is not caused by ganglion cell death alone, as approximately 30% of chorda tympani neurons survived into adulthood. Although the total field volume of intact gustatory nerves was not altered, the GSP volume and GSP-GL overlap increased in the dorsal NTS after CTX at P5, but not P10, demonstrating age-dependent plasticity. Our findings indicate that the developing gustatory system is highly plastic and simultaneously vulnerable to injury.

Reproductive Dysfunction from Exercise Training: The "Exercise-Hypogonadal Male Condition".

The objective of this short review is to discuss how exercise training in men can result in changes in the reproductive system similar to those observed in women who develop athletic amenorrhea or suffer the Female Athlete Triad. Men chronically exposed to training for endurance sports exhibit persistently reduced basal free and total testosterone concentrations without concurrent luteinizing hormone elevations. These men are deemed to have the "Exercise-Hypogonadal Male Condition" (EHMC). Broadly, dysfunction in the hypothalamic-pituitary-gonadal regulatory axis is associated with either of these states. In women this effect on the axis is linked to the existence of a low energy availability (LEA) state, research in men relative to LEA is ongoing. The exact physiological mechanism inducing the reduction of testosterone in these men is currently unclear but is postulated to be a dysfunction within the hypothalamic-pituitary-gonadal regulatory axis. The potential exists for the reduced testosterone concentrations within EHMC men to be disruptive and detrimental to some anabolic-androgenic testosterone-dependent physiological processes. Findings, while limited, suggest spermatogenesis problems may exist in some cases; thus, infertility risk in such men is a critical concern. Present evidence suggests the EHMC condition is limited to men who have been persistently involved in chronic endurance exercise training for an extended period of time, and thus is not a highly prevalent occurrence. Nevertheless, it is critical that endocrinologist and fertility clinicians become more aware of the existence of EHMC as a potential problem-diagnosis in their male patients who exercise.

El objetivo de esta breve revisión es describir cómo el entrenamiento físico en hombres puede provocar cambios en el sistema reproductivo similares a los observados en mujeres que desarrollan amenorrea atlética o manifiestan la tríada de la mujer atleta. Hombres expuestos sistemáticamente a entrenamientos para deportes de resistencia exhiben concentraciones de testosterona libre y basal reducidas, pero sin manifestar un aumento simultáneo de hormona luteinizante. Esta condición se denomina "hipogonadismo masculino producto del ejercicio" (EHMC, por su siglas en inglés). Ambos estados están asociados a una disfunción en el eje hipotalámico-hipofisario-gonadal. En las mujeres, la alteración del eje está vinculada a un estado de baja disponibilidad energética (BDE); en los hombres, la investigación relacionada con la BDE está en curso. El mecanismo fisiológico exacto que induce la reducción de testosterona en estos hombres aún no está claro, pero se postula que es una disfunción dentro del eje regulador hipotalámico-hipofisario-gonadal. Existe la posibilidad de que las bajas concentraciones de testosterona de los hombres con EHMC sean disruptivas y perjudiciales para algunos procesos fisiológicos anabólicoandrogénicos dependientes de testosterona. Los hallazgos, aunque limitados, sugieren que en algunos casos pueden existir problemas de espermatogénesis; por lo tanto, el riesgo de infertilidad en tales hombres es una preocupación crucial. La evidencia actual sugiere que el EHMC se limita a hombres que han estado involucrados en entrenamiento de resistencia de manera persistente y durante tiempo prolongado, por lo que el EHMC no es una condición prevalente. De todos modos, es fundamental que médicos endocrinólogos y especialistas en fertilidad estén atentos a la existencia del EHMC como potencial problema ­ y diagnostico ­ que pueden padecer sus pacientes deportistas varones.