Sweat Gland Density Research Articles

The effect of female breast surface area on heat-activated sweat gland density and output.

Female development includes significant morphological changes across the breast. Yet, whether differences in breast surface area (BrSA) modify sweat gland density and output remains unclear. The present study investigated the relationship between BrSA and sweat gland density and output in 22 young to middle-aged women (28 10years) of varying breast sizes (BrSA range: 147-561cm2) during a submaximal run in a warm environment (32 0.6°C; 53 1.7% relative humidity). Local sweat gland density and local sweat rate (LSR) above and below the nipple and at the bra triangle were measured. Expired gases were monitored for the estimation of evaporative requirements for heat balance (Ereq, in W/m2). Associations between BrSA and (i) sweat gland density; (ii) LSR; and (iii) sweat output per gland for the breast sites were determined via correlation and regression analyses. Our results indicated that breast sweat gland density decreased linearly as BrSA increased (r=-0.76, P<0.001), whereas sweat output per gland remained constant irrespective of BrSA (r=0.29, P=0.28). This resulted in LSR decreasing linearly as BrSA increased (r=-0.62, P=0.01). Compared to the bra triangle, the breast had a 64% lower sweat gland density (P<0.001), 83% lower LSR (P<0.001) and 53% lower output per gland (P<0.001). BrSA (R2=0.33, P=0.015) explained a greater proportion of variance in LSR than Ereq (in W/m2) (R2=0.07, P=0.538). These novel findings extend the known relationship between body morphology and sweat gland density and LSR, to the female breast. This knowledge could innovate user-centred design of sports bras by accommodating breast size-specific needs for sweat management, skin wetness perception and comfort.

Efficacy of spironolactone in treating hidradenitis suppurativa in women of childbearing age: a single-center retrospective analysis.

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent nodules that affect areas with a high density of apocrine sweat glands, such as the axillae and groin. Androgens are implicated in the pathophysiology of HS. Therefore, spironolactone, an antiandrogen therapy, is recommended. However, data on its use in women of childbearing age are limited, especially since its antiandrogenic effects may affect menstruation, fertility, and pubertal development. To evaluate the efficacy and safety of spironolactone in the treatment of hidradenitis suppurativa in women of childbearing age and to identify factors associated with treatment response. A retrospective analysis was conducted on female patients aged 12 to 50 with HS treated with spironolactone at Michigan Medicine dermatology clinics from 2000 to 2021. The patients' demographic data, HS characteristics, and spironolactone responses were examined. Statistical assessments were performed to determine the efficacy indicators. Of the 157 patients reviewed, 31 showed an improvement in treatment. Variables such as axillary involvement, previous treatment failures, and use of intralesional steroids were linked to a lack of improvement in spironolactone. Through adjusted multiple logistic regression analysis, a significant association was observed between improvement status and Hurley stage 3 (odds ratio = 0.15 [95% CI: 0.02-0.79], P = .036), suggesting that patients with Hurley stage 3 were 85% less likely to exhibit improvement in spironolactone therapy. The study's retrospective nature and reliance on single-center data can limit generalizability. The sample size is limited and therefore affects the study's statistical power. Thus, spironolactone may offer therapeutic benefits for HS in women of childbearing age. However, patients with severe disease (Hurley stage 3) had reduced response rates. Further prospective studies are recommended to validate these findings and determine the most suitable patient profile for spironolactone therapy for HS.

Aspects of the skin morphology in the sub-Antarctic fur seal Arctocephalus tropicalis

The present study examined whether sweat glands are present in the skin of sub-Antarctic fur seals, Arctocephalus tropicalis, using standard histological procedures and light microscopy. Aspects of the microanatomy and histology of skin were described to elucidate structure and function. Sweat glands were present both in the furred areas of the body trunk, as well as in naked skin areas of the flippers. The density of the apocrine sweat glands appeared higher in fur-covered areas than in naked areas, while the size of sweat glands was similar amongst naked and fur-covered skin. The superficial position of sweat glands in the dermis of naked skin areas and the large, coiled, tubular nature of the secretory portion seem to indicate sweat gland activity in contrast to the deep lying, narrow sweat glands in fur-covered areas.

Human glabrous skin contains crystallized urea dendriform structures in the stratum corneum which affect the hydration levels.

Glabrous skin is hair-free skin with a high density of sweat glands, which is found on the palms, and soles of mammalians, covered with a thick stratum corneum. Dry hands are often an occupational problem which deserves attention from dermatologists. Urea is found in the skin as a component of the natural moisturizing factor and of sweat. We report the discovery of dendrimer structures of crystalized urea in the stratum corneum of palmar glabrous skin using laser scanning microscopy. The chemical and structural nature of the urea crystallites was investigated in vivo by non-invasive techniques. The relation of crystallization to skin hydration was explored. We analysed the index finger, small finger and tenar palmar area of 18 study participants using non-invasive optical methods, such as laser scanning microscopy, Raman microspectroscopy and two-photon tomography. Skin hydration was measured using corneometry. Crystalline urea structures were found in the stratum corneum of about two-thirds of the participants. Participants with a higher density of crystallized urea structures exhibited a lower skin hydration. The chemical nature and the crystalline structure of the urea were confirmed by Raman microspectroscopy and by second harmonic generated signals in two-photon tomography. The presence of urea dendrimer crystals in the glabrous skin seems to reduce the water binding capacity leading to dry hands. These findings highlight a new direction in understanding the mechanisms leading to dry hands and open opportunities for the development of better moisturizers and hand disinfection products and for diagnostic of dry skin.

Variation in human functional eccrine gland density and its implications for the evolution of human sweating.

We aim to test three questions regarding human eccrine sweat gland density, which is highly derived yet poorly understood. First, is variation in functional eccrine gland density ("FED") explained by childhood climate, suggesting phenotypic plasticity? Second, is variation in FED explained by genetic similarity (a proxy for "geographic ancestry"), implying divergent evolutionary pathways in this trait of ancestral populations? Third, what is the relationship between FED and sweat production? To test questions one and two, we measured FED in 68 volunteers aged 18-39 with varied childhood climate regimes and geographic ancestries. To test question three, we compared sweat production to FED in our n=68 sample. In addition, we examined the relationship between FED and whole-body sweat loss during cycling in warm conditions using a sample of eight heat-acclimated endurance athletes. Interindividual variation in six-site FED was more than twofold, ranging from 60.9 to 132.7glands/cm2 . Variation in FED was best explained by body surface area and limb circumferences (negative associations) and poorly explained by childhood climatic conditions and genetic similarity. Pilocarpine-induced sweat production was unrelated to FED while whole-body sweat loss during cycling was significantly, though modestly, associated with FED. We hypothesize that gland-level phenotypic plasticity, rather than changes in eccrine gland density, was sufficient to permit thermal adaptation to novel environments as humans colonized the globe. Future research should measure effects of FED in dehydrated states and the relationship between FED and salt loss, and control for effects of microclimate to rule out phenotypic plasticity effects.

Physiological and Proteomic Responses of Dairy Buffalo to Heat Stress Induced by Different Altitudes.

Buffalo are mainly distributed in low-altitude (LA), medium-altitude (MA), and high-altitude (HA) regions characterised by different thermal and oxygen environments in Yunnan province, China. Due to black skin, sparse hair, and the low density of skin sweat glands, buffalo are more sensitive to heat stress. Here, we used data-independent acquisition (DIA) proteomics to reveal a broad spectrum of proteins that play roles in adaptation to the heat stress of buffalo raised at low altitude or hypoxia at high altitude. LA buffalo showed higher body temperatures than MA- and HA buffalo, and HA buffalo had higher levels of GSH and SOD and lower levels of ROS compared to LA and MA buffalo. In 33 samples, 8476 peptides corresponding to 666 high-confidence proteins were detected. The levels of circulating complement proteins in the immune pathways were lower in LA and MA buffalo than in HA buffalo. There were higher levels of alpha-1 acid glycoprotein in LA buffalo than in MA and HA buffalo. Relative to MA buffalo, levels of blood oxygen delivery proteins were higher in LA and HA buffalo. A higher abundance of apolipoproteins was detected in LA and MA buffalo than in HA buffalo. In summary, buffalo adopted similar adaptation strategies to oxidative stress induced by heat stress or hypoxia, including immunological enhancement, high efficiency of blood oxygen delivery, and the inhibition of lipid oxidation.

745 Regional expression of secreted WNT inhibitors dictates formation of hairless and poorly haired skin

Different regions of mammalian skin vary in characteristics such as thickness, and hair follicle and sweat gland presence, size and density, that are reflected in differential responses to injury and disease. Positional information resides in the upper dermis but the responsible molecular mechanisms are poorly understood. To uncover these, we carried out comparative scRNA-seq of mouse embryonic dorsal, ear and plantar skin. This revealed differential regional expression of several secreted Wnt inhibitors, including Dkk2 and Sostdc1, suggesting regional modulation of Wnt signaling as an important mechanism controlling skin heterogeneity. In line with this, we showed previously that Dkk2-null mice develop regenerative hair follicles in normally hairless plantar skin. However, hair follicles in other regions had normal density and size. Loss of Sostdc1 is known to cause ectopic hair formation in nipple skin, extra vibrissae, and larger hair follicle placodes in trunk skin. We hypothesized that Dkk2 and Sostdc1 function partially redundantly to control additional regional skin features. To test this, we generated mice lacking both inhibitors. Double mutants displayed elevated Wnt signaling in embryonic plantar and ear skin, increased formation of plantar hair compared with Dkk2 single mutants, and growth of abnormally dense, long, thick hair on the external ears. Thus, regional modulation of Wnt signaling controls both the formation of hairless versus hairy skin, and the size and density of hair follicles in haired skin. These data support a new paradigm in which, rather than being dictated by an activating dermal signal as postulated in classical models, hair follicle formation is a default pathway that is actively suppressed by secreted inhibitors in skin regions that lack hair follicles or are poorly haired.

Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With M1 Macrophage Polarization in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent abscesses, nodules, and sinus tracts in areas of high hair follicle and sweat gland density. These sinus tracts can present with purulent drainage and scar formation. Dysregulation of multiple immune pathways drives the complexity of HS pathogenesis and may account for the heterogeneity of treatment response in HS patients. Using transcriptomic approaches, including single-cell sequencing and protein analysis, we here characterize the innate inflammatory landscape of HS lesions. We identified a shared upregulation of genes involved in interferon (IFN) and antimicrobial defense signaling through transcriptomic overlap analysis of differentially expressed genes (DEGs) in datasets from HS skin, diabetic foot ulcers (DFUs), and the inflammatory stage of normal healing wounds. Overlap analysis between HS- and DFU-specific DEGs revealed an enrichment of gene signatures associated with monocyte/macrophage functions. Single-cell RNA sequencing further revealed monocytes/macrophages with polarization toward a pro-inflammatory M1-like phenotype and increased effector function, including antiviral immunity, phagocytosis, respiratory burst, and antibody-dependent cellular cytotoxicity. Specifically, we identified the STAT1/IFN-signaling axis and the associated IFN-stimulated genes as central players in monocyte/macrophage dysregulation. Our data indicate that monocytes/macrophages are a potential pivotal player in HS pathogenesis and their pathways may serve as therapeutic targets and biomarkers in HS treatment.

LB782 A retrospective case series of Ustekinumab therapy in patients with severe and recalcitrant Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by painful nodules and sinus tracts in areas of high sweat gland and hair follicle density, such as the axilla and groin. These debilitating features may impair quality of life and cause significant psychosocial burden. Though the pathophysiology of HS is complex and incompletely understood, various cytokines are under investigation as targets for biologic therapy. Adalimumab, a monoclonal antibody that targets tumor necrosis factor-a (TNF-a), is currently the only FDA-approved antibody therapy for HS.

Origins of the sweaty ape

Human Evolution Humans are unique mammals that lack hair in many parts of their body and have an increased capacity for sweating, which assists in thermoregulation, through eccrine sweat glands. Using a comparative genomics approach to study the regulation of genes involved in the development of eccrine sweat glands, Aldea et al. investigated noncoding genomic elements to determine the differences underlying the increased eccrine sweat gland density of humans relative to other primates and mice. They found that human-specific evolution in a noncoding enhancer, hECE18, likely increases gene expression of the Engrailed1 gene, which is required for the development of eccrine sweat glands. Furthermore, humanized hECE18 knock-in mice have an increased number of these glands, supporting the idea that this human-specific adaptation is a result of changes in the noncoding regulatory regions of proteins. Proc. Natl. Acad. Sci. U.S.A. 118 , e2021722118 (2021).

Power Spectrum Features of Acupoint Bioelectricity Signal

Background: Since the 1950s, many studies have been conducted on the electrical properties of acupuncture points (acupoints), especially their bio-resistance characteristics. Results of such studies have been inconclusive due to factors such as sweat gland density and compounding factors of applying electrical stimulation. In this study, a power spectrum instrument was used to assess the power spectrum and power of acupoints and non-acupoints without electrical stimulation. Using such instrumentation, specificity of electrical signals of acupoints was also explored. Methods: Thirty-six subjects (29 females, 7 males) participated in the study. Stainless steel acupuncture needles (diameter 0.35 mm, length 50 mm) were used. Five acupoints were tested: ST36, SP6, GB39, GB37, and KI9. Four control sites 0.5-1.0 cm adjacent to each acupoint were chosen. After needle insertion into the acupoint and control sites, the needles were attached to the power spectrum instrument to acquire any electrical signals. Acquire signals were analyzed using self-written software. Results: Power spectrum difference between acupoint and non-acupoint signals was 0-2 Hz. Results of t-test or signed rank sum test (α= 0.05) found that electrical signals between acupoints and non-acupoints were markedly different (P < 0.05). Conclusion: Acupoint bioelectricity signals are higher than adjacent non-acupoints. The most significant difference is distributed between 0 Hz to 2 Hz.

Repeated mutation of a developmental enhancer contributed to human thermoregulatory evolution

Humans sweat to cool their bodies and have by far the highest eccrine sweat gland density among primates. Humans' high eccrine gland density has long been recognized as a hallmark human evolutionary adaptation, but its genetic basis has been unknown. In humans, expression of the Engrailed 1 (EN1) transcription factor correlates with the onset of eccrine gland formation. In mice, regulation of ectodermal En1 expression is a major determinant of natural variation in eccrine gland density between strains, and increased En1 expression promotes the specification of more eccrine glands. Here, we show that regulation of EN1 has evolved specifically on the human lineage to promote eccrine gland formation. Using comparative genomics and validation of ectodermal enhancer activity in mice, we identified a human EN1 skin enhancer, hECE18. We showed that multiple epistatically interacting derived substitutions in the human ECE18 enhancer increased its activity compared with nonhuman ape orthologs in cultured keratinocytes. Repression of hECE18 in human cultured keratinocytes specifically attenuated EN1 expression, indicating this element positively regulates EN1 in this context. In a humanized enhancer knock-in mouse, hECE18 increased developmental En1 expression in the skin to induce the formation of more eccrine glands. Our study uncovers a genetic basis contributing to the evolution of one of the most singular human adaptations and implicates multiple interacting mutations in a single enhancer as a mechanism for human evolutionary change.

Power Spectrum Features of Acupoint Bioelectricity Signal.

Background Since the 1950s, many studies have been conducted on the electrical properties of acupuncture points (acupoints), especially their bio-resistance characteristics. Results of such studies have been inconclusive due to factors such as sweat gland density and compounding factors of applying electrical stimulation. In this study, a power spectrum instrument was used to assess the power spectrum and power of acupoints and nonacupoints without electrical stimulation. Using such instrumentation, specificity of electrical signals of acupoints was also explored. Methods Thirty-six subjects (29 females, 7 males) participated in the study. Stainless steel acupuncture needles (diameter 0.35 mm; length 50 mm) were used. Five acupoints were tested: ST 36, SP 6, GB 39, GB 37, and K I9. Four control sites 0.5–1.0 cm adjacent to each acupoint were chosen. After needle insertion into the acupoint and control sites, the needles were attached to the power spectrum instrument to acquire any electrical signals. Acquire signals were analyzed using self-written software. Results Power spectrum difference between acupoint and nonacupoint signals was 0–2 Hz. Results of t-test or signed rank sum test (α = 0.05) found that electrical signals between acupoints and nonacupoints were markedly different (P < 0.05). Conclusion Acupoint bioelectricity signals are higher than adjacent nonacupoints. The most significant difference is distributed between 0 Hz and 2 Hz.

Aging-related shift of eccrine sweat glands toward the skin surface due to tangling and rotation of the secretory ducts revealed by digital 3D skin reconstruction.

BackgroundSweat gland function deteriorates with aging, leading to loss of heat tolerance. However, it is unclear whether and how the structure of sweat glands changes during aging, because the 3D structure is complex and inaccessible.MethodsTo clarify age‐dependent changes in sweat glands, we developed a method for 3D structure analysis of sweat glands by means of X‐ray micro‐CT observation of human skin specimens followed by 3D digital reconstruction on computer (digital 3D skin).ResultsComparison of eccrine sweat glands of abdominal skin from young and old subjects showed that the density and volume of sweat glands do not change with aging. In contrast, the depth of the secretory coil from the skin surface is decreased in the aged group. Surprisingly, the secretory ducts appear tortuous or meandering though their length is unchanged. The secretory coils are located at the dermal‐adipose layer boundary in both groups, but the thickness of the dermal layer decreases with aging, and the depth of the coils is correlated with the dermal thickness.ConclusionOur results suggest that sweat glands twist and rotate with aging to maintain the position of the coil at the dermal‐adipose boundary, causing an overall shift toward the skin surface.

Design and Evaluation of an Electrodermal Activity Sensor (EDA) With Adaptive Gain

Electrodermal activity (EDA) is a physiological signal that can be measured non-intrusively and associated with the sympathetic nervous system, hence being widely used nowadays. Although multiple sensor designs have been proposed over the years, practical hardware limitations still persist, due to differences in the electrode materials used to interface with the body, sweat gland density at the recording sites, and variability in the overall electrical properties of the skin in-between users. This is particularly challenging when low resolution Analog-to-Digital Converters (ADC) are used, which, due to the proliferation of open source and low-cost hardware platforms, are currently widespread. In this article we present a design and experimental evaluation of a new circuit for EDA measurement with adaptive gain control, allowing the dynamic adaptation of the measurement range. The proposed circuit has shown comparable results to those obtained with a reference sensor, obtaining a mean correlation coefficient of 0.967, and proved to have superior performance in cases where the reference sensor would saturate.

789 Evolution of an Engrailed 1 enhancer underlies expanded sweat gland density of humans

789 Evolution of an Engrailed 1 enhancer underlies expanded sweat gland density of humans

Characterisation of a second gain of function EDAR variant, encoding EDAR380R, in East Asia

Ectodysplasin A1 receptor (EDAR) is a TNF receptor family member with roles in the development and growth of hair, teeth and glands. A derived allele of EDAR, single-nucleotide variant rs3827760, encodes EDAR:p.(Val370Ala), a receptor with more potent signalling effects than the ancestral EDAR370Val. This allele of rs3827760 is at very high frequency in modern East Asian and Native American populations as a result of ancient positive selection and has been associated with straighter, thicker hair fibres, alteration of tooth and ear shape, reduced chin protrusion and increased fingertip sweat gland density. Here we report the characterisation of another SNV in EDAR, rs146567337, encoding EDAR:p.(Ser380Arg). The derived allele of this SNV is at its highest global frequency, of up to 5%, in populations of southern China, Vietnam, the Philippines, Malaysia and Indonesia. Using haplotype analyses, we find that the rs3827760 and rs146567337 SNVs arose on distinct haplotypes and that rs146567337 does not show the same signs of positive selection as rs3827760. From functional studies in cultured cells, we find that EDAR:p.(Ser380Arg) displays increased EDAR signalling output, at a similar level to that of EDAR:p.(Val370Ala). The existence of a second SNV with partly overlapping geographic distribution, the same in vitro functional effect and similar evolutionary age as the derived allele of rs3827760, but of independent origin and not exhibiting the same signs of strong selection, suggests a northern focus of positive selection on EDAR function in East Asia.

Sex-related differences in sudomotor function in healthy early twenties focused on activated sweat gland density.

The purpose of this study was to quantitatively assess the difference in sudomotor function between healthy males and females in their early twenties by measuring skin surface area and activated sweat gland density (ASGD). The quantitative sudomotor axon reflex test (QSART), a method for evaluating autonomic nervous system activity, was used for quantification. In QSART, the sweat glands are activated directly or indirectly by the subcutaneous application of neurotransmitters, such as acetylcholine, through iontophoresis. This series of mechanisms is called the sudomotor axon reflex. After recording age, height, weight, and several measurements of the forearm, QSART was performed on 101 healthy controls aged 21-26 years to measure ASGD. The mean temperature and humidity on the measurement days were 11.4°C and 58.1% on May 3, 2018, and 14.7°C and 70.3% on May 10, 2018. The result of independent sample t-test showed higher ASGD in women (P < 0.05). The body surface area and the surface area of the forearms were higher in men (P < 0.001), but the number of activated sweat glands was not significantly different according to sex. The activated sweat gland counts of the body and forearms were analyzed through linear regression by age for males and females. Except for the activated sweat gland count of the male body, the analysis showed a tendency to decrease with increasing age but was not statistically significant in any case (P > 0.05). Showing insufficient coefficient of determination (R2), multiple regression analyses with sex and ages did not correct this insignificance between age and activated sweat gland count.

Nicotinic receptors modulate skin perfusion during normothermia, and have a limited role in skin vasodilatation and sweating during hyperthermia.

What is the central question of this study? What is the role of nicotinic receptors in the regulation of normothermic cutaneous blood flow and cutaneous vasodilatation and sweating during whole-body heating induced following resting in a non-heat-stress condition? What is the main finding and its importance? Nicotinic receptors modulated cutaneous vascular tone during rest in a non-heat-stress condition and in the early stage of heating, but they had a limited role in mediating cutaneous vasodilatation when core temperature increased>0.4°C. Further, the contribution of nicotinic receptors to sweating was negligible during whole-body heating. Our findings provide new insights into the role of nicotinic receptors in end-organ function of skin vasculature and sweat glands in humans. Nicotinic receptors are present in human skin including cutaneous vessels and eccrine sweat glands as well as peripheral nerves. We tested the hypothesis that nicotinic receptors do not contribute to the control of cutaneous vascular tone in the normothermic state, but are involved in mediating cutaneous vasodilatation and sweating during a whole-body passive heat stress in humans. We first performed a nicotinic receptor blocker verification protocol in six young adults (one female) wherein increases in cutaneous vascular conductance and sweating elicited by 10mm nicotine were blocked by administration of 500µm hexamethonium to confirm effective blockade. Thereafter, 12 young males participated in a passive heating protocol. After an instrumentation period in a non-heat-stress condition, participants rested for a 10min baseline period. Thereafter, oesophageal temperature was increased by 1.0°C using water-perfusion suits. Cutaneous vascular conductance, sweat rate, active sweat gland density and sweat output per individual gland were assessed with and without 500µm hexamethonium administered via intradermal microdialysis. Hexamethonium reduced cutaneous vascular conductance by 22-34% during normothermia and the early stage of heating. However, this effect was diminished as oesophageal temperature increased >0.4°C. Active sweat gland density was reduced by hexamethonium when oesophageal temperature was elevated by 0.4-0.6°C above baseline resting. However, this was paralleled by a marginal increase in sweat gland output. Consequently, sweat rate remained unchanged. We showed that nicotinic receptors modulate cutaneous perfusion during normothermia and the early stage of heating, but not when core temperature increases >0.4°C. Additionally, they play a limited role in mediating sweating during heating.

Diversity and evolution of human eccrine sweat gland density.

The human eccrine sweat gland is central to the evolution of the human genus, permitting an enormous thermoregulatory sweating capacity that was essential to the human niche of high physical activity in open, hot, semi-arid environments. Despite a century of research inventorying the structure and function of eccrine glands and the physiological responses of human heat acclimation, we do not have a clear understanding of how intraspecific differences in eccrine density affect thermoregulation. Similarly, existing data does not comprehensively catalogue modern human diversity in this trait, nor do we understand the relative influences of evolutionary forces and phenotypic plasticity in shaping this diversity.