SnapShot: Hormones of the gastrointestinal tract.

Specialized endocrine cells secrete a variety of peptide hormones all along the gastrointestinal (GI) tract, making it one of the largest endocrine organs in the body. Nutrients and developmental and neural cues trigger the secretion of gastrointestinal (GI) hormones from specialized endocrine cells along the GI tract. These hormones act in target tissues to facilitate digestion and regulate energy homeostasis. This SnapShot summarizes the production and functions of GI hormones.

Hormonal control of stem cell systems.

Many organs respond to physiological challenges by changing tissue size or composition. Such changes may originate from tissue-specific stem cells and their supportive environment (niche). The endocrine system is a major effector and conveyor of physiological changes and as such could alter stem cell behavior in various ways. In this review, we examine how hormones affect stem cell biology in four different organs: the ovary, intestine, hematopoietic system, and mammary gland. Hormones control every stage of stem cell life, including establishment, expansion, maintenance, and differentiation. The effects can be cell autonomous or non-cell autonomous through the niche. Moreover, a single hormone can affect different stem cells in different ways or affect the same stem cell differently at various developmental times. The vast complexity and diversity of stem cell responses to hormonal cues allow hormones to coordinate the body's reaction to physiological challenges.

Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa.

Because of the compartmentalization of disciplines that shaped the academic landscape of biology and biomedical sciences in the past, physiological systems have long been studied in isolation from each other. This has particularly been the case for the immune system. As a consequence of its ties with pathology and microbiology, immunology as a discipline has largely grown independently of physiology. Accordingly, it has taken a long time for immunologists to accept the concept that the immune system is not self-regulated but functions in close association with the nervous system. These associations are present at different levels of organization. At the local level, there is clear evidence for the production and use of immune factors by the central nervous system and for the production and use of neuroendocrine mediators by the immune system. Short-range interactions between immune cells and peripheral nerve endings innervating immune organs allow the immune system to recruit local neuronal elements for fine tuning of the immune response. Reciprocally, immune cells and mediators play a regulatory role in the nervous system and participate in the elimination and plasticity of synapses during development as well as in synaptic plasticity at adulthood. At the whole organism level, long-range interactions between immune cells and the central nervous system allow the immune system to engage the rest of the body in the fight against infection from pathogenic microorganisms and permit the nervous system to regulate immune functioning. Alterations in communication pathways between the immune system and the nervous system can account for many pathological conditions that were initially attributed to strict organ dysfunction. This applies in particular to psychiatric disorders and several immune-mediated diseases. This review will show how our understanding of this balance between long-range and short-range interactions between the immune system and the central nervous system has evolved over time, since the first demonstrations of immune influences on brain functions. The necessary complementarity of these two modes of communication will then be discussed. Finally, a few examples will illustrate how dysfunction in these communication pathways results in what was formerly considered in psychiatry and immunology to be strict organ pathologies.

Neuronal and hormonal control of Ca2+ signalling in exocrine glands: insight from in vivo studies.

Fluid and enzyme secretion from exocrine glands is initiated by Ca2+ signalling in acinar cells and is activated by external neural or hormonal signals. A wealth of information has been derived from studies in acutely isolated exocrine cells but Ca2+ signalling has until recently not been studied in undisrupted intact tissue in live mice. Our in vivo observations using animals expressing genetically encoded Ca2+ indicators in specific cell types in exocrine glands revealed both similarities to and differences from the spatiotemporal characteristics previously reported in isolated cells. These in vivo studies facilitate further understanding of how both neuronal and hormonal input shapes Ca2+ signalling events in a physiological setting and how these signals are translated into the stimulation of fluid secretion and exocytosis.

Fear Memory.

Fear memory is the best-studied form of memory. It was thoroughly investigated in the past 60 years mostly using two classical conditioning procedures (contextual fear conditioning and fear conditioning to a tone) and one instrumental procedure (one-trial inhibitory avoidance). Fear memory is formed in the hippocampus (contextual conditioning and inhibitory avoidance), in the basolateral amygdala (inhibitory avoidance), and in the lateral amygdala (conditioning to a tone). The circuitry involves, in addition, the pre- and infralimbic ventromedial prefrontal cortex, the central amygdala subnuclei, and the dentate gyrus. Fear learning models, notably inhibitory avoidance, have also been very useful for the analysis of the biochemical mechanisms of memory consolidation as a whole. These studies have capitalized on in vitro observations on long-term potentiation and other kinds of plasticity. The effect of a very large number of drugs on fear learning has been intensively studied, often as a prelude to the investigation of effects on anxiety. The extinction of fear learning involves to an extent a reversal of the flow of information in the mentioned structures and is used in the therapy of posttraumatic stress disorder and fear memories in general.

Laminin-binding integrins are essential for the maintenance of functional mammary secretory epithelium in lactation.

Integrin dimers α3/ß1, α6/ß1 and α6/ß4 are the mammary epithelial cell receptors for laminins, which are major components of the mammary basement membrane. The roles of specific basement membrane components and their integrin receptors in the regulation of functional gland development have not been analyzed in detail. To investigate the functions of laminin-binding integrins, we obtained mutant mice with mammary luminal cell-specific deficiencies of the α3 and α6 integrin chains generated using the Cre-Lox approach. During pregnancy, mutant mice displayed decreased luminal progenitor activity and retarded lobulo-alveolar development. Mammary glands appeared functional at the onset of lactation in mutant mice; however, myoepithelial cell morphology was markedly altered, suggesting cellular compensation mechanisms involving cytoskeleton reorganization. Notably, lactation was not sustained in mutant females, and the glands underwent precocious involution. Inactivation of the p53 gene rescued the growth defects but did not restore lactogenesis in mutant mice. These results suggest that the p53 pathway is involved in the control of mammary cell proliferation and survival downstream of laminin-binding integrins, and underline an essential role of cell interactions with laminin for lactogenic differentiation.

A nonparametric test of group distributional differences for hierarchically clustered functional data.

Biological sex and gender are critical variables in biomedical research, but are complicated by the presence of sex-specific natural hormone cycles, such as the estrous cycle in female rodents, typically divided into phases. A common feature of these cycles are fluctuating hormone levels that induce sex differences in many behaviors controlled by the electrophysiology of neurons, such as neuronal membrane potential in response to electrical stimulus, typically summarized using a priori defined metrics. In this paper, we propose a method to test for differences in the electrophysiological properties across estrous cycle phase without first defining a metric of interest. We do this by modeling membrane potential data in the frequency domain as realizations of a bivariate process, also depending on the electrical stimulus, by adopting existing methods for longitudinal functional data. We are then able to extract the main features of the bivariate signals through a set of basis function coefficients. We use these coefficients for testing, adapting methods for multivariate data to account for an induced hierarchical structure that is a product of the experimental design. We illustrate the performance of the proposed approach in simulations and then apply the method to experimental data.

Integrating animal development: How hormones and metabolism regulate developmental transitions and brain formation.

Our current knowledge on how individual tissues or organs are formed during animal development is considerable. However, the development of each organ does not occur in isolation and thus their formation needs to be done in a coordinated manner. This coordination is regulated by hormones, systemic signals that instruct the simultaneous development of all organs and direct tissue specific developmental programs. In addition, multi- and individual-organ development requires the integration of the nutritional state of the animal, since this affects nutrient availability necessary for the progression of development and growth. Variations in the nutritional state of the animal are normal during development, as the sources and access to nutrients greatly differ depending on the animal stage. Furthermore, adversities of the external environment also exert major alterations in extrinsic nutritional conditions. Thus, both in normal and malnutrition circumstances, the animal needs to trigger metabolic changes to maintain energy homeostasis and sustain growth and development. This metabolic flexibility is mediated by hormones, that drive both developmental encoded metabolic transitions throughout development and adaptation responses according to the nutritional state of the animal. This review aims to provide a comprehensive summary of the current knowledge of how endocrine regulation coordinates multi-organ development by orchestrating metabolic transitions and how it integrates metabolic adaptation responses to starvation. We also focus on the particular case of brain development, as it is extremely sensitive to hormonally induced metabolic changes. Finally, we discuss how brain development is prioritized over the development of other organs, as its growth can be spared from nutrient deprivation.

The Pregnancy Pickle: Evolved Immune Compensation Due to Pregnancy Underlies Sex Differences in Human Diseases.

We hypothesize that, ancestrally, sex-specific immune modulation evolved to facilitate survival of the pregnant person in the presence of an invasive placenta and an immunologically challenging pregnancy - an idea we term the 'pregnancy compensation hypothesis' (PCH). Further, we propose that sex differences in immune function are mediated, at least in part, by the evolution of gene content and dosage on the sex chromosomes, and are regulated by reproductive hormones. Finally, we propose that changes in reproductive ecology in industrialized environments exacerbate these evolved sex differences, resulting in the increasing risk of autoimmune disease observed in females, and a counteracting reduction in diseases such as cancer that can be combated by heightened immune surveillance. The PCH generates a series of expectations that can be tested empirically and that may help to identify the mechanisms underlying sex differences in modern human diseases.

Seasonal reproduction and gonadal function: a focus on humans starting from animal studies.

Photoperiod impacts reproduction in many species of mammals. Mating occurs at specific seasons to achieve reproductive advantages, such as optimization of offspring survival. Light is the main regulator of these changes during the photoperiod. Seasonally breeding mammals detect and transduce light signals through extraocular photoreceptor, regulating downstream melatonin-dependent peripheral circadian events. In rodents, hormonal reduction and gonadal atrophy occur quickly and consensually with short-day periods. It remains unclear whether photoperiod influences human reproduction. Seasonal fluctuations of sex hormones have been described in humans, although they seem to not imply adaptative seasonal pattern in human gonads. This review discusses current knowledge about seasonal changes in the gonadal function of vertebrates, including humans. The photoperiod-dependent regulation of hypothalamic-pituitary-gonadal axis, as well as morphological and functional changes of the gonads is evaluated herein. Endocrine and morphological variations of reproductive functions, in response to photoperiod, are of interest as they may reflect the nature of past population selection for adaptative mechanisms that occurred during evolution.

A mating-induced reproductive gene promotes Anopheles tolerance to Plasmodium falciparum infection.

Anopheles mosquitoes have transmitted Plasmodium parasites for millions of years, yet it remains unclear whether they suffer fitness costs to infection. Here we report that the fecundity of virgin and mated females of two important vectors-Anopheles gambiae and Anopheles stephensi-is not affected by infection with Plasmodium falciparum, demonstrating that these human malaria parasites do not inflict this reproductive cost on their natural mosquito hosts. Additionally, parasite development is not impacted by mating status. However, in field studies using different P. falciparum isolates in Anopheles coluzzii, we find that Mating-Induced Stimulator of Oogenesis (MISO), a female reproductive gene strongly induced after mating by the sexual transfer of the steroid hormone 20-hydroxyecdysone (20E), protects females from incurring fecundity costs to infection. MISO-silenced females produce fewer eggs as they become increasingly infected with P. falciparum, while parasite development is not impacted by this gene silencing. Interestingly, previous work had shown that sexual transfer of 20E has specifically evolved in Cellia species of the Anopheles genus, driving the co-adaptation of MISO. Our data therefore suggest that evolution of male-female sexual interactions may have promoted Anopheles tolerance to P. falciparum infection in the Cellia subgenus, which comprises the most important malaria vectors.

Changes of lipoprotein(a) levels with endogenous steroid hormones.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an LDL-like molecule that is likely causal for cardiovascular events and Lp(a) variability has been shown to be mostly of genetic origin. Exogenous hormones (hormone replacement therapy) seem to influence Lp(a) levels, but the impact of endogenous hormone levels on Lp(a) is still unknown. The aim of the study was to assess the effect of endogenous steroid hormone metabolites on Lp(a). METHODS: Lipoprotein(a) levels were measured in 1,021 participants from the Swiss Kidney Project on Genes in Hypertension, a family-based, multicentre, population-based prospective cohort study. Endogenous levels of 28 steroid hormone precursors were measured in 24-h urine collections from 883 individuals. Of the participants with Lp(a) data, 1,011 participants had also genotypes available. RESULTS: The participants had an average age of 51 years and 53% were female. Median Lp(a) levels were 62 mg/L, and the 90th percentile was 616 mg/L. The prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. Forty-three per cent of Lp(a) variability was explained respectively by: age (2%, p < .001), LDL-C (1%, p = .001), and two SNPs (39%, p value<2⋅10-16 ). Of the 28 endogenous steroid hormones assessed, androstenetriol, androsterone, 16α-OH-DHEA and estriol were nominatively associated with serum Lp(a) levels in univariable analyses and explained 0.4%-1% of Lp(a) variability, but none of them reached significance in multivariable models. CONCLUSIONS: In this contemporary population-based study, the prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. The effect of endogenous steroid hormone levels of Lp(a) variability was small at best, suggesting a negligible impact on the wide range of Lp(a) variability.

Revisiting the Stress Concept: Implications for Affective Disorders.

Over the last 50 years, the concept of stress has evolved significantly, and our understanding of the underlying neurobiology has expanded dramatically. Rather than consider stress biology to be relevant only under unusual and threatening conditions, we conceive of it as an ongoing, adaptive process of assessing the environment, coping with it, and enabling the individual to anticipate and deal with future challenges. Though much remains to be discovered, the fundamental neurocircuitry that underlies these processes has been broadly delineated, key molecular players have been identified, and the impact of this system on neuroplasticity has been well established. More recently, we have come to appreciate the critical interaction between the brain and the rest of the body as it pertains to stress responsiveness. Importantly, this system can become overloaded due to ongoing environmental demands on the individual, be they physical, physiological, or psychosocial. The impact of this overload is deleterious to brain health, and it results in vulnerability to a range of brain disorders, including major depression and cognitive deficits. Thus, stress biology is one of the best understood systems in affective neuroscience and is an ideal target for addressing the pathophysiology of many brain-related diseases. The story we present began with the discovery of glucocorticoid receptors in hippocampus and has extended to other brain regions in both animal models and the human brain with the further discovery of structural and functional adaptive plasticity in response to stressful and other experiences.

Bilirubin as a metabolic hormone: the physiological relevance of low levels.

Recent research on bilirubin, a historically well-known waste product of heme catabolism, suggests an entirely new function as a metabolic hormone that drives gene transcription by nuclear receptors. Studies are now revealing that low plasma bilirubin levels, defined as "hypobilirubinemia," are a possible new pathology analogous to the other end of the spectrum of extreme hyperbilirubinemia seen in patients with jaundice and liver dysfunction. Hypobilirubinemia is most commonly seen in patients with metabolic dysfunction, which may lead to cardiovascular complications and possibly stroke. We address the clinical significance of low bilirubin levels. A better understanding of bilirubin's hormonal function may explain why hypobilirubinemia might be deleterious. We present mechanisms by which bilirubin may be protective at mildly elevated levels and research directions that could generate treatment possibilities for patients with hypobilirubinemia, such as targeting of pathways that regulate its production or turnover or the newly designed bilirubin nanoparticles. Our review here calls for a shift in the perspective of an old molecule that could benefit millions of patients with hypobilirubinemia.

Influence of Bowel Habit and Hormonal Changes on the Development of Hemorrhoidal Disease During Pregnancy and the Postdelivery Period: A Prospective Cohort Study.

BACKGROUND: Hemorrhoidal disease in women during pregnancy is common in clinical practice. However, prospective data on its real prevalence and women's demographics are scarce. OBJECTIVE: The aim of this study was to determine the prevalence of hemorrhoidal disease during pregnancy and to assess its impact on quality of life. In addition, this study aimed to identify the relationship between patients' characteristics, bowel habits, hormonal changes, and the presence of symptomatic hemorrhoids. DESIGN: This is a prospective longitudinal cohort study. SETTING: This study was conducted in the Obstetrics Department for pregnancy follow-up. PATIENTS: The patients evaluated were a cohort of pregnant women. INTERVENTION: The study was designed to follow a homogeneous cohort of women for 15 months. Visits took place in the first and third trimesters of pregnancy, and 3 and 6 months after delivery. Women's demographics (age, medical history, bowel habit, Bristol stool scale) and serum determination of pregnancy-related hormones (estrogen, progesterone, and relaxin) were determined. MAIN OUTCOME MEASURES: The primary outcome was the development of hemorrhoidal disease. RESULTS: Overall, 109 women (mean age, 31.2 ± 5.4 years) were included in the study. The prevalence of symptoms and physical findings of hemorrhoidal disease was present in 11% in the first trimester, 23% in the third trimester, 36.2% at 1 month after delivery, and 16.9% at 3 months after delivery. A medical history of hemorrhoidal disease was significantly associated with the diagnosis of hemorrhoids in the first trimester (p < 0.0001) and third trimester (p = 0.005). Symptoms of constipation were associated with this clinical disorder in the first trimester (p = 0.011) and the third trimester of pregnancy (p = 0.022). No association was found between hormonal changes and the development of hemorrhoidal disease. LIMITATIONS: A larger sample would provide more information. CONCLUSIONS: The prevalence of women with hemorrhoidal disease increases during pregnancy and after delivery. A history of hemorrhoidal disease and constipation is significantly associated with the diagnosis of symptomatic hemorrhoidal disease. See Video Abstract at http://links.lww.com/DCR/B504. INFLUENCIA DEL HBITO INTESTINAL Y LOS CAMBIOS HORMONALES EN EL DESARROLLO DE LA ENFERMEDAD HEMORROIDAL DURANTE EL EMBARAZO Y EL PERODO POSTERIOR AL PARTO UN ESTUDIO DE COHORTE PROSPECTIVO: ANTECEDENTES:La enfermedad hemorroidal en mujeres durante el embarazo es común en la práctica clínica. Sin embargo, hay escasos datos prospectivos sobre su prevalencia real y la demografía de las mujeres.OBJETIVO:El objetivo fue determinar la prevalencia de enfermedad hemorroidal durante el embarazo y evaluar su impacto en la calidad de vida. Además, identificar la relación entre las características de los pacientes, los hábitos intestinales, los cambios hormonales y la presencia de hemorroides sintomáticas.DISEÑO:Estudio prospectivo de cohorte longitudinal.AJUSTE:Este estudio se realizó en el Departamento de Obstetricia para el seguimiento del embarazo.PACIENTES:Una cohorte de mujeres embarazadas.INTERVENCIÓN:El estudio se diseñó para realizar un seguimiento de una cohorte homogénea de mujeres durante 15 meses. Las visitas se realizaron en el primer y tercer trimestre del embarazo, y a los 3 y 6 meses después del parto. Se determinaron los datos demográficos de las mujeres (edad, antecedentes médicos, hábito intestinal, escala de heces de Bristol) y la determinación sérica de hormonas relacionadas con el embarazo (estrógeno, progesterona y relaxina).PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue el desarrollo de enfermedad hemorroidal.RESULTADOS:Se incluyó en el estudio a 109 mujeres (edad media, 31,2 ± 5,4 años). La prevalencia de síntomas y hallazgos físicos de enfermedad hemorroidal estuvo presente en 11% en el primer trimestre, 23% en el tercer trimestre, 36,2% 1 mes después del parto y 16,9% 3 meses después del parto. Un historial médico previo de enfermedad hemorroidal se asoció significativamente con el diagnóstico de hemorroides en el primer trimestre (p <0,0001) y tercer trimestre (p = 0,005). Los síntomas de estreñimiento se asociaron con este trastorno clínico en el primer trimestre (p = 0,011) y el tercer trimestre del embarazo (p = 0,022), respectivamente. No se encontró asociación entre los cambios hormonales y el desarrollo de enfermedad hemorroidal.LIMITACIONES:Una muestra más grande proporcionaría más información.CONCLUSIONES:La prevalencia de mujeres con enfermedad hemorroidal aumentó durante el embarazo y el posparto. El antecedente de enfermedad hemorroidal y estreñimiento se asociaron significativamente con el diagnóstico de enfermedad hemorroidal sintomática. Consulte Video Resumen en http://links.lww.com/DCR/B504.

Relationship between betacoronaviruses and the endocrine system: a new key to understand the COVID-19 pandemic-A comprehensive review.

BACKGROUND: A new harmful respiratory disease, called COVID-19 emerged in China in December 2019 due to the infection of a novel coronavirus, called SARS-Coronavirus 2 (SARS-CoV-2), which belongs to the betacoronavirus genus, including SARS-CoV-1 and MERS-CoV. SARS-CoV-2 shares almost 80% of the genome with SARS-CoV-1 and 50% with MERS-CoV. Moreover, SARS-CoV-2 proteins share a high degree of homology (approximately 95%) with SARS-CoV-1 proteins. Hence, the mechanisms of SARS-Cov-1 and SARS-Cov-2 infection are similar and occur via binding to ACE2 protein, which is widely distributed in the human body, with a predominant expression in endocrine tissues including testis, thyroid, adrenal and pituitary. PURPOSE: On the basis of expression pattern of the ACE2 protein among different tissues, similarity between SARS-Cov-1 and SARS-Cov-2 and the pathophysiology of COVID-19 disease, we aimed at discussing, after almost one-year pandemic, about the relationships between COVID-19 infection and the endocrine system. First, we discussed the potential effect of hormones on the susceptibility to COVID-19 infection; second, we examined the evidences regarding the effect of COVID-19 on the endocrine system. When data were available, a comparative discussion between SARS and COVID-19 effects was also performed. METHODS: A comprehensive literature search within Pubmed was performed. This review has been conducted according to the PRISMA statements. RESULTS: Among 450, 100 articles were selected. Tissue and vascular damages have been shown on thyroid, adrenal, testis and pituitary glands, with multiple alterations of endocrine function. CONCLUSION: Hormones may affect patient susceptibility to COVID-19 infection but evidences regarding therapeutic implication of these findings are still missing. SARS and COVID-19 may affect endocrine glands and their dense vascularization, impairing endocrine system function. A possible damage of endocrine system in COVID-19 patients should be investigated in both COVID-19 acute phase and recovery to identify both early and late endocrine complications that may be important for patient's prognosis and well-being after COVID-19 infection.

[Hormonal influence on hearing]. / Hormonelle Beeinflussung des Hörvermögens.

BACKGROUND: Hearing loss leads to impairments in communication, social interactions, and cognitive functions. This renders early treatment particularly important. A causal therapy is not yet available. Human and animal studies have shown that certain hormones can have a positive effect on hearing. OBJECTIVE: This review provides an overview of the effects of various hormones on hearing and describes the potential benefit for future therapeutic approaches. MATERIALS AND METHODS: A systematic literature review of reviews dealing with the effects of various hormones on hearing in humans and animals published in PubMed between 2015 and 2020 was conducted. RESULTS: Hormones may mediate antiapoptotic effects on structure-relevant cells of the cochlea and auditory pathway, and may influence hair cell functionality or the electrolyte balance of the endo- and perilymph. Current research focuses on glucocorticoids; the mineral corticoid aldosterone; the sex hormones estrogen, progesterone, and testosterone; the growth hormones GH (growth hormone) and IGF­1 (insulin-like growth factor 1); thyroid hormones; and insulin. Study results are still inconsistent at this time, but various hormones appear to represent a possible future treatment option for acute hearing loss. Long-term hormone treatment, which would be necessary particularly in the case of age-related hearing loss, does not currently represent a sensible course of action due to the side effect profile of the systemic treatment/lack of practicable topical application options. CONCLUSION: The mode of action of hormones is complex. Whether they can be used in the future for individualized treatment of patients with acute hearing impairment requires further investigation.

Development of human ectocervical tissue models with physiologic endocrine and paracrine signaling†.

There is a shortage of research models that adequately represent the unique mucosal environment of human ectocervix, limiting development of new therapies for treating infertility, infection, or cancer. We developed three microphysiologic human ectocervix models to study hormone action during homeostasis. First, we reconstructed ectocervix using decellularized extracellular matrix scaffolds, which supported cell integration and could be clinically useful. Secondly, we generated organotypic systems consisting of ectocervical explants co-cultured with murine ovaries or cycling exogenous hormones, which mimicked human menstrual cycles. Finally, we engineered ectocervix tissue consisting of tissue-specific stromal-equivalents and fully-differentiated epithelium that mimicked in vivo physiology, including squamous maturation, hormone response, and mucin production, and remained viable for 28 days in vitro. The localization of differentiation-dependent mucins in native and engineered tissue was identified for the first time, which will allow increased efficiency in mucin targeting for drug delivery. In summary, we developed and characterized three microphysiologic human ectocervical tissue models that will be useful for a variety of research applications, including preventative and therapeutic treatments, drug and toxicology studies, and fundamental research on hormone action in a historically understudied tissue that is critical for women's health.

Endocrinology and immunology of acne: Two sides of the same coin.

Current experimental research on acne pathophysiology has revealed a more complicated background than the classically reported four-factor aetiology. Cells of the pilosebaceous unit, which represent the template for the development of acne lesions, seem to be parallelly affected by endocrinological/metabolic factors as well as inflammatory/immunological ones that cooperate in sebocyte differentiation and lipogenesis. Indeed, the unique programme of sebocyte terminal differentiation and death, the so called holocrine secretion, is influenced by inflammatory and metabolic (lipid) signalling with common denominator the selective regulation of peroxisome proliferator-activated receptors. Autophagy provides substrates for energy generation and biosynthesis of new cell structure proteins contributing to the normally increased sebaceous gland metabolic functions, which are also regulated by extracellular calcium signalling, essential lipids and hormones. The ultimate differentiation product of human sebocytes, sebum, co-regulates the inflammatory sebocyte status. Sebum composition is controlled among others by Propionibacterium acnes and other bacteria, sexual hormones, neuropeptides, endogenous opioids and environmental agents, which may function as endocrine disruptors. Diet may also be an important source of substrates for the synthesis of pro-inflammatory and anti-inflammatory sebaceous lipids. Sebum changes might induce inflammation and initiate underlying immune mechanisms leading to acne lesions. Current new therapeutic efforts on acne concentrate on anti-inflammatory/immunologically active concepts, which are able to regulate sebaceous lipogenesis. At last, current molecular studies based on published molecular data sets confirmed the major role of inflammation in acne development.

An updated field guide for snark hunting: Comparative contributions to behavioral neuroendocrinology in the era of model organisms.

Studying neuroendocrine behavioral regulatory mechanisms in a variety of species across vertebrate groups is critical for determining how they work in natural contexts, how they evolved, and ultimately what can be generalized from them, potentially even to humans. All of the above are difficult, at best, if work within our field is exclusively done in traditional laboratory organisms. The importance of comparative approaches for understanding the relationships between hormones and behavior has been recognized and advocated for since our field's inception through a series of papers centered upon a poetic metaphor of Snarks and Boojums, all of which have articulated the benefits that come from studying a diverse range of species and the risks associated with a narrow focus on "model organisms." This mini-review follows in the footsteps of those powerful arguments, highlighting some of the comparative work since the latest interactions of the metaphor that has shaped how we think about three major conceptual frameworks within our field, two of them formalized - the Organization/Activation Model of sexual differentiation and the Social Brain Network - and one, context-dependency, that is generally associated with virtually all modern understandings of how hormones affect behavior. Comparative approaches are broadly defined as those in which the study of mechanism is placed within natural and/or evolutionary contexts, whether they directly compare different species or not. Studies are discussed in relation to how they have either extended or challenged generalities associated with the frameworks, how they have shaped subsequent work in model organisms to further elucidate neuroendocrine behavioral regulatory mechanisms, and how they have stimulated work to determine if and when similar mechanisms influence behavior in our own species.