Evaluation of a polymer-coated nanoparticle cream formulation of resiniferatoxin for the treatment of painful diabetic peripheral neuropathy.

ABSTRACT: Painful diabetic peripheral neuropathy (PDPN) is one of the major complications of diabetes. Currently, centrally acting drugs and topical analgesics are used for treating PDPN. These drugs have adverse effects; some are ineffective, and treatment with opioids is associated with use dependence and addiction. Recent research indicates that transient receptor potential vanilloid 1 (TRPV1) expressed in the peripheral sensory nerve terminals is an emerging target to treat pain associated with PDPN. Block of TRPV1 ion channel with specific antagonists, although effective as an analgesic, induced hyperthermia in clinical trials. However, TRPV1 agonists are useful to treat pain by virtue of their ability to cause Ca 2+ influx and subsequently leading to nerve terminal desensitization. Here, we report the effectiveness of an ultrapotent TRPV1 agonist, resiniferatoxin (RTX) nanoparticle, in a topical formulation (RTX-cream; RESINIZIN) that alleviates pain associated with DPN in animal models of diabetes. Resiniferatoxin causes nerve terminal depolarization block in the short term, which prevents pain during application and leading to nerve terminal desensitization/depletion in the long term resulting in long-lasting pain relief. Application of RTX cream to the hind limbs suppresses thermal hyperalgesia in streptozotocin-induced diabetic rats and mini pigs without any adverse effects as compared with capsaicin at therapeutic doses, which induces intense pain during application. Resiniferatoxin cream also decreases the expression of TRPV1 in the peripheral nerve endings and suppresses TRPV1-mediated calcitonin gene-related peptide release in the skin samples of diabetic rats and mini pigs. Our preclinical data confirm that RTX topical formulation is an effective treatment option for PDPN.

Dietary Fatty Acid Composition Impacts the Fatty Acid Profiles of Different Regions of the Bovine Brain.

Fatty acid composition across functional brain regions was determined in bovine brains collected from cattle that were provided supplements of calcium salts containing either palm or fish oil. The Angus cattle were divided into two groups, with one group offered the supplement of calcium salts of palm oil and the other offered the calcium salts of fish oil (n = 5 females and n = 5 males/supplement) for 220 days. These supplements to the basal forage diet were provided ad libitum as a suspension in dried molasses. The fish oil exclusively provided eicosapentaenoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3). The functional regions were dissected from the entire brains following commercial harvest. While the cattle provided diets supplemented with the calcium salts of palm oil had increased (p < 0.01) liver concentrations of C18:1 n-9, C18:2 n-6, and arachidonic acid, the fish-oil-supplemented cattle had greater (p < 0.01) concentrations of liver EPA, DHA, and C18:3 n-3. In the brain, DHA was the most abundant polyunsaturated fatty acid. In the amygdala, pons, frontal lobe, internal capsule, and sensory cortex, DHA concentrations were greater (p < 0.05) in the brains of the cattle fed fish oil. Differences among the supplements were small, indicating that brain DHA content is resistant to dietary change. Arachidonic acid and C22:4 n-6 concentrations were greater across the regions for the palm-oil-supplemented cattle. EPA and C22:5 n-3 concentrations were low, but they were greater across the regions for the cattle fed fish oil. The effects of sex were inconsistent. The fatty acid profiles of the brain regions differed by diet, but they were similar to the contents reported for other species.

Medroxyprogesterone acetate in reindeer bulls: testes histology, cfos activity in the brain, breeding success, and semen quality.

A previous study reported that a 400-mg dose of medroxyprogesterone acetate (MPA) reduced male reindeer aggression and blocked development of secondary sexual characteristics but did not completely impair fertility. Here we have repeated that protocol in two separate trials. In 2017, tissues and blood samples, collected from MPA and control (CTL) reindeer bulls, euthanized at 30 and 60 d post-treatment were used to evaluate testes histology and morphometrics, cfos activity in the brain and androgen levels. While testes weight tended to decline from August to September in both groups, indices of spermatogenesis remained high. By September, indices of spermatogenesis were declining in both groups with sperm density lower (P = 0.05) in MPA compared to CTL bulls. Aug CTL bulls had the highest concentrations of androstenedione (A4) (P = 0.009) and testosterone (T) (P = 0.08), whereas these androgens were baseline in Aug MPA bulls. By September, A4 and T levels in CTL bulls declined to levels measured in MPA bulls. Cfos activity had a greater number (P = 0.02) of cfos positive neurons in the central amygdala in MPA compared to CTL bulls, suggesting a heightened fear response among the MPA bulls. In the second trial (2019), MPA-treated bulls, with (E, n = 4) and without (IE, n = 4) breeding experience, were blood sampled at key points from July through September when they were put in individual harems with estrous-synchronized cows. Concentrations of T were greatest (P < 0.001) among E bulls prior to MPA treatment but 1 mo after treatment, both T and A4 were baseline in all eight reindeer. Semen collected by electroejaculation at 60 d post-MPA treatment revealed only minor differences in sperm abnormalities between E and IE bulls using both fresh and frozen/thawed semen. Only three bulls (2 E and 1 IE) sired offspring. Breeding success was not related to previous breeding experience, body weight, or bull age. The failure of some MPA bulls to breed appears to be a behavioral, not a physiological, limitation. Limited application of MPA is clearly a useful tool for managing rut-aggression in non-breeding reindeer. However, the possibility that semen could be collected from MPA-treated bulls using restraint and mild sedation rather than general anesthesia should be investigated. This could improve the quality of semen collection while enhancing the safety of both handlers and animals.

A single 400 mg dose of MPA given to reindeer bulls just before the onset of rut eliminates aggressive behavior and suppresses androgen concentrations without dramatic differences in the gross or histological structure of the testes within the first 30 d of treatment. By 60 d post-treatment, there is evidence of smaller testes size and decreased sperm density in treated bulls. However, if given the opportunity, some treated bulls can still successfully breed. Breeding success in MPA bulls was not solely related to previous breeding experience, body weight, or bull age. Androgen concentrations and semen characteristics did not vary with previous breeding experience. Failure of some treated bulls to breed appears to be a behavioral limitation. Differences in brain activity between control and treated bulls were few except for increased cfos activity in the central amygdala of MPA bulls, potentially increasing the fear response in these reindeer.

Changes in Bone Mineral Density and Serum Lipids across the First Postpartum Year: Effect of Aerobic Fitness and Physical Activity.

This study evaluated the changes in bone mineral density (BMD) and serum lipids across the first postpartum year in lactating women compared to never-pregnant controls, and the influence of physical activity (PA). The study also explored whether N-telopeptides, pyridinoline, and deoxypyridinoline in urine serve as biomarkers of bone resorption. A cohort of 18 initially lactating postpartum women and 16 never pregnant controls were studied. BMD (dual energy X-ray absorptiometry), serum lipid profiles, and PA (Baecke PA Questionnaire) were assessed at baseline (4-6 weeks postpartum), 6 months, and 12 months. Postpartum women lost 5.2 ± 1.4 kg body weight and BMD decreased by 1.4% and 3.1% in the total body and dual-femur, respectively. Furthermore, BMDdid not show signs of rebound. Lipid profiles improved, with increases in high-density lipoprotein-cholesterol (HDL-C) and decreases in low-density lipoprotein cholesterol (LDL-C) and the cholesterol/HDL-C ratio at 12 months (vs. baseline). These changes were not influenced by lactation, but the fall the Cholesterol/HDL-C ratio was influenced by leisure-time (p = 0.051, time X group) and sport (p = 0.028, time effect) PA. The decrease in BMD from baseline to 12 months in total body and dual femur, however, was greater in those who continued to breastfeed for a full year compared to those who stopped at close to 6 months. Urinary markers of bone resorption, measured in a subset of participants, reflect BMD loss, particularly in the dual-femur, and may reflect changes bone resorption before observed changes in BMD. Results provide support that habitual postpartum PA may favorably influence changes in serum lipids but not necessarily BMD. The benefit of exercise and use of urinary biomarkers of bone deserves further exploration.

Reproductive performance of rams that failed breeding soundness evaluation: The need to reconsider the evaluation.

Breeding soundness evaluations for sires closely followed the introduction of electro-ejaculation as a tool for the measurement of bull fertility in 1950. Quickly following the establishment of bull breeding soundness evaluations, similar criteria were established for rams. It is intuitive that structural soundness, body condition, testes size and palpable consistency, as well as semen parameters are important for fertility. The value of a breeding soundness evaluation as evidenced by ram fertility is lacking. Rams (n = 55) were subjected to an industry standard breeding soundness evaluation (BSE). Regardless of the BSE outcome rams were placed in a competitive breeding environment (approximately 1:30 ram:ewe). Genomic DNA was extracted from rams and approximately one-third of the lambs (n = 468) and their dams (n = 379). Microsatellite markers were used to determine parentage. Rams that passed the BSE (n = 37) did not (P = 0.86) sire more lambs (8.7 ± 1.7) than rams that failed BSE (n = 18; 8.2 ± 2.3). Both rams that passed or failed the BSE had zero identified offspring (32.4% of rams with passed; 22.2% of rams with failed) and did not differ (P = 0.54) by BSE status. Notably, the ram with the greatest number of identified offspring had a failed BSE siring more than three times the 99% confidence interval for expected number of lambs. While this small study does not warrant wholesale dismissal of BSE, it does give pause to the ram BSE and perhaps what constitutes a satisfactory breeder should be reconsidered.

Reflection of Dietary Iodine in the 24 h Urinary Iodine Concentration, Serum Iodine and Thyroglobulin as Biomarkers of Iodine Status: A Pilot Study.

BACKGROUND: The iodine status of the US population is considered adequate, but subpopulations remain at risk for iodine deficiency and a biomarker of individual iodine status has yet to be determined. The purpose of this study was to determine whether a 3 day titration diet, providing known quantities of iodized salt, is reflected in 24 h urinary iodine concentration (UIC), serum iodine, and thyroglobulin (Tg). METHODS: A total of 10 participants (31.3 ± 4.0 years, 76.1 ± 6.3 kg) completed three, 3 day iodine titration diets (minimal iodine, US RDA, (United States Recommended Daily Allowance), and 3× RDA). The 24 h UIC, serum iodine, and Tg were measured following each diet. The 24 h UIC and an iodine-specific food frequency questionnaire (FFQ) were completed at baseline. RESULTS: UIC increased an average of 19.3 µg/L for every gram of iodized salt consumed and was different from minimal to RDA (p = 0.001) and RDA to 3× RDA diets (p = 0.04). Serum iodine was different from RDA to 3× RDA (p = 0.006) whereas Tg was not responsive to diet. Baseline UIC was associated with iodine intake from milk (r = 0.688, p = 0.028) and fish/seafood (r = 0.646, p = 0.043). CONCLUSION: These results suggest that 24 h UIC and serum iodine may be reflective of individual iodine status and may serve as biomarkers of iodine status.

Appetite-Regulating Hormones in Human Milk: A Plausible Biological Factor for Obesity Risk Reduction?

BACKGROUND: Human milk contains appetite-regulating hormones that may influence infant growth and obesity risk. RESEARCH AIMS: We evaluated whether leptin, peptide tyrosine-tyrosine (PYY), glucagon-like peptide-1 (GLP-1), and ghrelin concentrations in human milk (1) changed during feeding (from foremilk to hindmilk) and during the first 6 months of infancy; (2) were explained by maternal factors; and (3) were associated with infant anthropometrics and growth. METHODS: Mother-infant dyads (N = 22) participated. Samples of foremilk and hindmilk at 1 month postpartum were collected and analyzed for leptin, PYY, GLP-1, and ghrelin via radioimmunoassay and milkfat percentage estimated via creamatocrit. Samples were also collected in mothers (n = 15) who breastfed through 6 months. Anthropometrics were obtained on all mother-infant dyads at 1 month and all infants at 6 months and 12 months. RESULTS: At 1 month, milk GLP-1 and milkfat concentration increased from foremilk to hindmilk (p ≤ .05) while leptin and PYY concentrations remained stable during feeding. Milk hormone concentrations and milkfat tended to decline overtime, with lower leptin, PYY, and ghrelin at 6 months versus 1 month (p < .05). At 1 month, milk leptin and milkfat content were associated with maternal markers of adiposity (r = 0.49-0.78, p < .001); whereas, milk PYY was correlated with maternal serum PYY concentration (r = 0.672, p = .001). Average 1-month milk concentrations of GLP-1 and leptin were negatively associated with weight-for-age z-scores at 6 months (r = -0.46, p < .05) and 12 months (r = -0.49, p < .05), respectively. CONCLUSION: The content of certain appetite-regulating hormones in human milk may be influenced by maternal factors and play a role in infant growth; much needs to be learned about their role in the obesity protection of breastfed infants.

Vitamin D Synthesis Following a Single Bout of Sun Exposure in Older and Younger Men and Women.

Older adults are frequently cited as an at-risk population for vitamin D deficiency that may in part be due to decreased cutaneous synthesis, a potentially important source of cholecalciferol (vitamin D3). Previous studies found that cutaneous D3 production declines with age; however, most studies have been conducted ex vivo or in the photobiology lab. The purpose of this study was to characterize the response of vitamin D metabolites following a 30-min bout of sun exposure (15-min each to the dorsal and ventral sides) at close to solar noon in younger and older adults. METHODS: 30 healthy individuals with skin type II/III were recruited; a younger cohort, aged 20-37 (n = 18) and an older cohort (n = 12), age 51-69 years. Exposure was at outer limits of sensible sun exposure designed to enhance vitamin D synthesis without increasing risk of photo ageing and non-melanoma skin cancer. Serum D3 concentration was measured at baseline, 24, 48 and 72 h post-exposure. Serum 25(OH)D was measured at baseline and 72 h post-exposure plus 168 h post-exposure in the older cohort. RESULTS: D3 increased in response to sun exposure (time effect; p = 0.002) with a trend for a difference in D3 between cohorts (time*group; p = 0.09). By regression modeling of continuous data, age accounted for 20% of the variation in D3 production. D3 production decreased by 13% per decade. Despite changes in D3, however, serum 25(OH)D did not change from baseline to 72 or 168 h post exposure (p > 0.10). CONCLUSIONS: Serum D3 concentration increased significantly in response to outdoor sun exposure in younger and older adults. While ageing may dampen cutaneous synthesis, sunlight exposure is still a significant source of vitamin D3.

TRPM8 as the rapid testosterone signaling receptor: Implications in the regulation of dimorphic sexual and social behaviors.

Testosterone regulates dimorphic sexual behaviors in all vertebrates. However, the molecular mechanism underlying these behaviors remains unclear. Here, we report that a newly identified rapid testosterone signaling receptor, Transient Receptor Potential Melastatin 8 (TRPM8), regulates dimorphic sexual and social behaviors in mice. We found that, along with higher steroid levels in the circulation, TRPM8-/- male mice exhibit increased mounting frequency indiscriminate of sex, delayed sexual satiety, and increased aggression compared to wild-type controls, while TRPM8-/- females display an increased olfaction-exploratory behavior. Furthermore, neuronal responses to acute testosterone application onto the amygdala were attenuated in TRPM8-/- males but remained unchanged in females. Moreover, activation of dopaminergic neurons in the ventral tegmental area following mating was impaired in TRPM8-/- males. Together, these results demonstrate that TRPM8 regulates dimorphic sexual and social behaviors, and potentially constitutes a signalosome for mediation of sex-reward mechanism in males. Thus, deficiency of TRPM8 might lead to a delayed sexual satiety phenomenon.

ASAS-SSR Triennial Reproduction Symposium: Looking Back And Moving Forward-How Reproductive Physiology Has Evolved: Male reproductive behavior: sensory signaling in the brain of low-performing domestic rams.

Rams are selected for genetic traits a producer desires to propagate in his flock. Even though practically all sheep are naturally bred, rams are rarely evaluated for expression of sexual interest or behavior. Research at the U.S. Sheep Experiment Station reported that the proportion of rams with limited interest in ewes was nearly 30% of the total number of breeding rams. Breeding soundness tested rams with low sexual interest sire less than 16% of the lamb crop. Although producers recognize the problem, their usual solution is to increase the number of rams in breeding flocks decreasing the risk of open ewes. Increased costs and a lack of genetic progress are clearly important considerations, but the biological question as to what controls sexual interest remains intriguing. Circulating concentrations of testosterone do not differ by sexual interest among rams. However, following exposure to estrous ewes, sexually active, but not inactive, rams exhibit an increase in LH pulsatile activity, a biological response to sexual stimuli. This begs the question as to whether sexually inactive rams recognize sexual cues. Using c fos activity as an indicator of neural activity, differences in the olfactory pathway were compared among sexually active and inactive rams. Differences in fos activity were not detected in the olfactory bulb or medial amygdala. However, sexually inactive rams had lower fos activity in the central amygdala, bed nucleus of the stria terminalis, and medial preoptic area of the hypothalamus following exposure to sexual evocative olfactory stimuli. This suggests sexually inactive rams detect olfactory cues but have decreased vigilance to sensory stimuli and a muted response to sexual signals in areas of the brain required for the execution of sexual performance. With the amygdala receiving and integrating sensory signals from many areas of the brain, sexually inactive rams may lack normal reward mechanisms contributing to their lack of sexual interest. Rams with limited sexual interest have decreased dopamine synthesis and a lower expression of dopamine D2 receptors following exposure to sexual stimuli. Thus, a tempered reward pathway in combination with decreased vigilance and sensory processing in the amygdala may reduce stimulation and/or responsiveness in areas of the brain required for expression of sexual behavior.

Sun exposure in pigs increases the vitamin D nutritional quality of pork.

There is a high prevalence of vitamin D insufficiency and deficiency worldwide likely because of both limited sun-exposure and inadequate dietary intake. Meat, including pork, is not typically considered a dietary source of vitamin D, possibly because of management practices that raise pigs in confinement. This experiment determined the vitamin D content of loin and subcutaneous adipose tissue in sun-exposed finisher pigs. Two separate groups of pigs were used. The first group (28 white Landrace-Duroc) was assigned at random to either sunlight exposure (SUN) in spring and summer or confinement per standard practice (Control). The second (24 Yorkshire-Duroc-Landrace) underwent the same exposure protocol but was exposed in summer and fall or assigned to control (Control). A subsample of five SUN and four Control pigs, matched for weight and body condition score, was selected for slaughter from each group. Pigs (n = 10 SUN, n = 8 Control) had blood drawn for analysis of 25(OH)D3 concentration before/after sun exposure or control, and tissue samples were taken at slaughter for analysis of tissue vitamin D3 and 25(OH)D3 concentration. Three random samples from a single loin chop and surrounding adipose were collected and analyzed. Serum concentrations of 25(OH)D3 did not differ (P≥0.376) between treatments prior to sun exposure in either group, but was increased (time*treatment interaction, P<0.001) with SUN exposure. Total vitamin D content (D3 plus 25(OH)D3) of loin tissue was increased (P < 0.001) with sun exposure and averaged 0.997±0.094 µg/100g and 0.348±0.027 µg/100g for sun and control pigs, respectively. While exposure to sunlight increased (P = 0.003) tissue content of 25(OH) D in subcutaneous adipose tissue, vitamin D3 content was similar between treatments (P = 0.56). Sunlight exposure in pigs increased the vitamin D content of loin, and may provide an additional source of dietary vitamin D.

Vitamin D and Weight Cycling: Impact on Injury, Illness, and Inflammation in Collegiate Wrestlers.

This study explored the link between vitamin D status and frequency of skin infections, inflammation, and injury in college wrestlers during an academic year. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) (n = 19), plasma cytokine (TNF-α, IL-6, IL-10) (n = 18) concentrations, and body weight/composition were measured and injury/illness/skin infection data were collected in fall, winter, and spring. RESULTS: In the fall, 74% of wrestlers had vitamin D concentrations <32 ng/mL which increased to 94% in winter and spring. Wrestlers lost an average of 3.4 ± 3.9 kg (p < 0.001) during the season with corresponding decreases in fat mass and increases in lean mass (p < 0.01). An inverse association between 25(OH)D concentrations and total body mass and body fat percentage was observed at all-time points (p < 0.01). Concentrations of cytokines were highly variable among individuals and did not change across time (p > 0.05). Correlations between vitamin D status, cytokines, or frequency of illness, injury, or skin infections were not observed. CONCLUSIONS: A high prevalence of vitamin D insufficiency (<32 ng/mL) and deficiency (<20 ng/mL) was observed in wrestlers and was associated with higher adiposity. It remains unclear if higher vitamin D status would reduce injury, illness, and skin infection risk.

Do Lactation-Induced Changes in Ghrelin, Glucagon-Like Peptide-1, and Peptide YY Influence Appetite and Body Weight Regulation during the First Postpartum Year?

To determine whether fasting and meal-induced appetite-regulating hormones are altered during lactation and associated with body weight retention after childbearing, we studied 24 exclusively breastfeeding women (BMI = 25.2 ± 3.6 kg/m(2)) at 4-5 weeks postpartum and 20 never-pregnant controls (BMI = 24.0 ± 3.1 kg/m(2)). Ghrelin, PYY, GLP-1, and appetite ratings were measured before/and 150 minutes after a standardized breakfast and 60 minutes after an ad libitum lunch. Body weight/composition were measured at 6 and 12 months. Fasting and area under-the-curve responses for appetite-regulating hormones did not differ between lactating and control groups; ghrelinacyl, however, tended to track higher after the standardized breakfast in lactating women and was higher (p < 0.05) after the ad libitum lunch despite a 24% higher energy intake (p < 0.05). By 12 months, lactating women lost 5.3 ± 2.2 kg (n = 18), whereas control women (n = 15) remained weight stable (p = 0.019); fifteen of the lactating women returned to within ±2.0 kg of prepregnancy weight but three retained >6.0 kg. The retainers had greater (p < 0.05) postmeal ghrelin rebound responses following breakfast. Overall these studies do not support the hypothesis that appetite-regulating hormones are altered during lactation and associated with postpartum weight retention. Altered ghrelin responses, however, deserve further exploration.

No Effect of Exercise Intensity on Appetite in Highly-Trained Endurance Women.

In endurance-trained men, an acute bout of exercise is shown to suppress post-exercise appetite, yet limited research has examined this response in women. The purpose of this study was to investigate the effect of exercise intensity on appetite and gut hormone responses in endurance-trained women. Highly-trained women (n = 15, 18-40 years, 58.4 ± 6.4 kg, VO2MAX = 55.2 ± 4.3 mL/kg/min) completed isocaloric bouts (500 kcals or 2093 kJ) of moderate-intensity (MIE, 60% VO2MAX) and high-intensity (HIE, 85% VO2MAX) treadmill running at the same time of day, following a similar 48-h diet/exercise period, and at least 1-week apart. Blood was drawn pre-exercise (baseline), immediately post-exercise and every 20-min for the next 60-min. Plasma concentrations of acylated ghrelin, PYY3-36, GLP-1 and subjective appetite ratings via visual analog scale (VAS) were assessed at each time point. Acylated ghrelin decreased (p = 0.014) and PYY3-36 and GLP-1 increased (p = 0.036, p < 0.0001) immediately post-exercise, indicating appetite suppression. VAS ratings of hunger and desire to eat decreased immediately post-exercise (p = 0.0012, p = 0.0031, respectively), also indicating appetite suppression. There were no differences between exercise intensities for appetite hormones or VAS. Similar to males, post-exercise appetite regulatory hormones were altered toward suppression in highly-trained women and independent of energy cost of exercise. Results are important for female athletes striving to optimize nutrition for endurance performance.

Presence and dynamics of leptin, GLP-1, and PYY in human breast milk at early postpartum.

OBJECTIVE: The presence of appetite hormones, namely glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and leptin in breast milk may be important in infant feeding regulation and infant growth. This study evaluated whether concentrations of GLP-1, PYY, and leptin change across a single feeding (from fore- to hindmilk), and are associated with maternal and infant anthropometrics. DESIGN AND METHODS: Thirteen postpartum women (mean ± SD: 25.6 ± 4.5 years, 72.0 ± 11.9 kg) provided fore- and hindmilk samples 4-5 weeks after delivery and underwent measurements of body weight and composition by Dual X-ray Absorptiometry. GLP-1, PYY, and leptin concentrations were measured using radioimmunoassay, and milk fat content was determined by creamatocrit. RESULTS: Concentration of GLP-1 and content of milk fat was higher in hindmilk than foremilk (P ≤ 0.05). PYY and leptin concentrations did not change between fore- and hindmilk. Both leptin concentration and milk fat content were correlated with indices of maternal adiposity, including body mass index (r = 0.65-0.85, P < 0.02), and fat mass (r = 0.65-0.84, P < 0.02). Hindmilk GLP-1 was correlated with infant weight gain from birth to 6 months (r = -0.67, P = 0.034). CONCLUSION: The presence of appetite hormones in breast milk may be important in infant appetite and growth regulation.

Influence of running and walking on hormonal regulators of appetite in women.

Nine female runners and ten walkers completed a 60 min moderate-intensity (70% VO(2)max) run or walk, or 60 min rest in counterbalanced order. Plasma concentrations of the orexogenic peptide ghrelin, anorexogenic peptides peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and appetite ratings were measured at 30 min interval for 120 min, followed by a free-choice meal. Both orexogenic and anorexogenic peptides were elevated after running, but no changes were observed after walking. Relative energy intake (adjusted for cost of exercise/rest) was negative in the meal following running (-194 ± 206 kcal) versus walking (41 ± 196 kcal) (P = 0.015), although both were suppressed (P < 0.05) compared to rest (299 ± 308 and 284 ± 121 kcal, resp.). The average rate of change in PYY and GLP-1 over time predicted appetite in runners, but only the change in GLP-1 predicted hunger (P = 0.05) in walkers. Results provide evidence that exercise-induced alterations in appetite are likely driven by complex changes in appetite-regulating hormones rather than change in a single gut peptide.

Wired on steroids: sexual differentiation of the brain and its role in the expression of sexual partner preferences.

The preference to seek out a sexual partner of the opposite sex is robust and ensures reproduction and survival of the species. Development of female-directed partner preference in the male is dependent on exposure of the developing brain to gonadal steroids synthesized during critical periods of sexual differentiation of the central nervous system. In the absence of androgen exposure, a male-directed partner preference develops. The development and expression of sexual partner preference has been extensively studied in rat, ferret, and sheep model systems. From these models it is clear that gonadal testosterone, often through estrogenic metabolites, cause both masculinization and defeminization of behavior during critical periods of brain development. Changes in the steroid environment during these critical periods result in atypical sexual partner preference. In this manuscript, we review the major findings which support the hypothesis that the organizational actions of sex steroids are responsible for sexual differentiation of sexual partner preferences in select non-human species. We also explore how this information has helped to frame our understanding of the biological influences on human sexual orientation and gender identity.