More Like this

1. Steroid hormone concentrations in milk predict sex‐specific offspring growth in a nonhuman primate

   https://doi.org/10.1002/ajhb.23315  

   Petrullo, Lauren ; Hinde, Katie ; Lu, Amy ( August 2019 , American Journal of Human Biology)

   In humans and other mammals, maternal hormones are transferred to offspring during lactation via milk and may regulate postnatal development, including the pace of early growth. Here, we used a nonhuman primate model to test the hypotheses that milk cortisol and dehydroepiandrosterone‐sulfate (DHEAS) concentrations reflect maternal characteristics, and that changes in these hormones across lactation are associated with early postnatal growth rates.

   Demographic information, morphometrics, and milk samples were collected from rhesus macaque mothers and their infants at the California National Primate Research Center in Davis, California. Using linear models, we examined the relationship between maternal traits and milk hormone concentrations (N = 104 females) and explored the effect of milk hormones on the rate of offspring growth (N = 72 mother‐infant dyads), controlling for available milk energy.

   Contrary to previous studies, we found that milk cortisol concentrations were categorically higher in multiparous females than in primiparous females. However, milk DHEAS concentrations decreased with maternal parity. Neither milk cortisol nor DHEAS were related to maternal rank. Finally, changes in milk hormones predicted offspring growth in a sex‐specific and temporal manner: increases in cortisol from peak to late lactation predicted faster female growth, and increases in DHEAS concentrations from early to peak and peak to late lactation predicted faster male growth.

   Our findings shed light on how hormonal components of milk have sex‐specific effects on offspring growth during early postnatal life with varying temporal windows of sensitivity.

    

   more » « less
2. Hormonal Dysregulation and Unbalanced Specialized Pro‐Resolving Mediator Biosynthesis Contribute toward Impaired B Cell Outcomes in Obesity

   https://doi.org/10.1002/mnfr.201900924  

   Crouch, Miranda ; Al‐Shaer, Abrar ; Shaikh, Saame Raza ( April 2020 , Molecular Nutrition & Food Research)

   Diet‐induced obesity is associated with impaired B‐cell‐driven humoral immunity, which coincides with chronic inflammation and has consequences for responses to infections and vaccinations. Key nutritional, cellular, and molecular mechanisms by which obesity may impair aspects of humoral immunity such as B cell development, class switch recombination, and formation of long‐lived antibody secreting cells are reviewed. A key theme to emerge is the central role of white adipose tissue on the formation and function of pro‐inflammatory B cell subsets that exacerbate insulin resistance. The underlying role of select hormones such as leptin is highlighted, which may be driving the formation of pro‐inflammatory B cells in the absence of antigen stimulation. This review also extensively covers the regulatory role of lipid metabolites such as prostaglandins and specialized pro‐resolving mediators (SPMs) that are synthesized from polyunsaturated fatty acids. Notably, SPM biosynthesis is impaired in obesity and contributes toward impaired antibody production. Future directions for research, including avenues for therapeutic intervention, are included.

    

   more » « less
3. Human‐like adrenal development in wild chimpanzees: A longitudinal study of urinary dehydroepiandrosterone‐sulfate and cortisol

   https://doi.org/10.1002/ajp.23064  

   Sabbi, Kris H. ; Muller, Martin N. ; Machanda, Zarin P. ; Otali, Emily ; Fox, Stephanie A. ; Wrangham, Richard W. ; Emery Thompson, Melissa ( November 2019 , American Journal of Primatology)

   The development of the adrenal cortex varies considerably across primates, being most conspicuous in humans, where a functional zona reticularis–the site of dehydroepiandrosterone‐sulfate (DHEA/S) production–does not develop until middle childhood (5–8 years). Prior reports suggest that a human‐like adrenarche, associated with a sharp prepubertal increase in DHEA/S, may only occur in the genusPan. However, the timing and variability in adrenarche in chimpanzees remain poorly described, owing to the lack of longitudinal data, or data from wild populations. Here, we use urine samples from East African chimpanzees (Pan troglodytes schweinfurthii)collected over 20 years at Kanyawara in Kibale National Park, Uganda, to trace the developmental trajectories of DHEAS (n = 1,385 samples, 53 individuals) and cortisol (n = 12,726 samples, 68 individuals). We used generalized additive models (GAM) to investigate the relationship between age, sex, and hormone levels. Adrenarche began earlier in chimpanzees (~2–3 years) compared with what has been reported in humans (6–8 years) and, unlike humans, male and female chimpanzees did not differ significantly in the timing of adrenarche nor in DHEAS concentrations overall. Similar to what has been reported in humans, cortisol production decreased through early life, reaching a nadir around puberty (8–11 years), and a sex difference emerged with males exhibiting higher urinary cortisol levels compared with females by early adulthood (15–16 years). Our study establishes that wild chimpanzees exhibit a human‐like pattern of cortisol production during development and corroborates prior reports from captive chimpanzees of a human‐like adrenarche, accompanied by significant developmental increases in DHEAS. While the role of these developmental hormone shifts are as yet unclear, they have been implicated in stages of rapid behavioral development once thought unique to humans, especially in regard to explaining the divergence of female and male social behavior before pubertal increases in gonadal hormones.

    

   more » « less
4. Resistance to the sympathoexcitatory effects of insulin and leptin in late pregnant rats

   https://doi.org/10.1113/JP278282  

   Shi, Zhigang ; Hansen, Kim M. ; Bullock, Kristin M. ; Morofuji, Yoichi ; Banks, William A. ; Brooks, Virginia L. ( July 2019 , The Journal of Physiology)

   Pregnancy increases sympathetic nerve activity (SNA), although the mechanisms responsible for this remain unknown. We tested whether insulin or leptin, two sympathoexcitatory hormones increased during pregnancy, contribute to this.

   Transport of insulin across the blood–brain barrier in some brain regions, and into the cerebrospinal fluid (CSF), was increased, although brain insulin degradation was also increased. As a result, brain and CSF insulin levels were not different between pregnant and non‐pregnant rats.

   The sympathoexcitatory responses to insulin and leptin were abolished in pregnant rats.

   Blockade of arcuate nucleus insulin receptors did not lower SNA in pregnant or non‐pregnant rats.

   Collectively, these data suggest that pregnancy renders the brain resistant to the sympathoexcitatory effects of insulin and leptin, and that these hormones do not mediate pregnancy‐induced sympathoexcitation. Increased muscle SNA stimulates glucose uptake. Therefore, during pregnancy, peripheral insulin resistance coupled with blunted insulin‐ and leptin‐induced sympathoexcitation ensures adequate delivery of glucose to the fetus.

   Pregnancy increases basal sympathetic nerve activity (SNA), although the mechanism responsible for this remains unknown. Insulin and leptin are two sympathoexcitatory hormones that increase during pregnancy, yet, pregnancy impairs central insulin‐ and leptin‐induced signalling. Therefore, to test whether insulin or leptin contribute to basal sympathoexcitation or, instead, whether pregnancy induces resistance to the sympathoexcitatory effects of insulin and leptin, we investigated α‐chloralose anaesthetized late pregnant rats, which exhibited increases in lumbar SNA (LSNA), splanchnic SNA and heart rate (HR) compared to non‐pregnant animals. In pregnant rats, transport of insulin into cerebrospinal fluid and across the blood–brain barrier in some brain regions increased, although brain insulin degradation was also increased; brain and cerebrospinal fluid insulin levels were not different between pregnant and non‐pregnant rats. Althoughi.c.v.insulin increased LSNA and HR and baroreflex control of LSNA and HR in non‐pregnant rats, these effects were abolished in pregnant rats. In parallel, pregnancy completely prevented the actions of leptin with respect to increasing lumbar, splanchnic and renal SNA, as well as baroreflex control of SNA. Blockade of insulin receptors (with S961) in the arcuate nucleus, the site of action of insulin, did not decrease LSNA in pregnant rats, despite blocking the effects of exogenous insulin. Thus, pregnancy is associated with central resistance to insulin and leptin, and these hormones are not responsible for the increased basal SNA of pregnancy. Because increases in LSNA to skeletal muscle stimulates glucose uptake, blunted insulin‐ and leptin‐induced sympathoexcitation reinforces systemic insulin resistance, thereby increasing the delivery of glucose to the fetus.

    

   more » « less
5. Closed-Loop Fuzzy Energy Regulation in Patients With Hypercortisolism via Inhibitory and Excitatory Intermittent Actuation

   https://doi.org/10.3389/fnins.2021.695975  

   Fekri Azgomi, Hamid ; Hahn, Jin-Oh ; Faghih, Rose T. ( August 2021 , Frontiers in Neuroscience)

   Hypercortisolism or Cushing's disease, which corresponds to the excessive levels of cortisol hormone, is associated with tiredness and fatigue during the day and disturbed sleep at night. Our goal is to employ a wearable brain machine interface architecture to regulate one's energy levels in hypercortisolism. In the present simulation study, we generate multi-day cortisol profile data for ten subjects both in healthy and disease conditions. To relate an internal hidden cognitive energy state to one's cortisol secretion patterns, we employ a state-space model. Particularly, we consider circadian upper and lower bound envelopes on cortisol levels, and timings of hypothalamic pulsatile activity underlying cortisol secretions as continuous and binary observations, respectively. To estimate the hidden cognitive energy-related state, we use Bayesian filtering. In our proposed architecture, we infer one's cognitive energy-related state using wearable devices rather than monitoring the brain activity directly and close the loop utilizing fuzzy control. To model actuation in the real-time closed-loop architecture, we simulate two types of medications that result in increasing and decreasing the energy levels in the body. Finally, we close the loop using a knowledge-based control approach. The results on ten simulated profiles verify how the proposed architecture is able to track the energy state and regulate it using hypothetical medications. In a simulation study based on experimental data, we illustrate the feasibility of designing a wearable brain machine interface architecture for energy regulation in hypercortisolism. This simulation study is a first step toward the ultimate goal of managing hypercortisolism in real-world situations. 

   more » « less