October 25,2023
Research field: Life science and medicine
Keywords: Sweat glands,Gap junctions, hyperhidrosis, antiperspirant

Uncovering the Mechanism of Sweat GlandContractions During Sweating and Discovering a
New Antiperspirant Agent— Awarded the Best Poster Presentation at IFSCC 2023 —Potential Applications in the Development of Next-Generation
Antiperspirants and Research on Sweating Dysfunction【Key Research Findings】
The mechanism by which sweat glands contract
during sweating has been elucidated.

Connexins*1 that form gap junctions*2 areabundant in myoepithelial cells, which areresponsible for sweat gland contractions, andthese gap junctions are significantly involvedin sweat gland contractions during sweating.

A gap junction blocker and its analoguemonoammonium glycyrrhizate (GMA)*3 inhibit
thermogenic (heat-induced) and psychogenic(mental stress-induced) sweating in humans.

The findings of this study will be utilized in the development of next-generation
antiperspirant technologies directly targeting sweat gland contractions during sweating tocontrol perspiration beyond current methods. They are also expected to be applied toresearch on sweating disorders such as hyperhidrosis.

•Overview
Our research group led by Fumitaka Fujita, Guest Professor of the Laboratory of Advanced

Cosmetic Science (Joint Research Program with Mandom), Graduate School of PharmaceuticalSciences, Osaka University; Kiyotoshi Sekiguchi, Professor of the Division for Matrixome
Research and Application (endowed by Mandom), Institute for Protein Research, Osaka
University; Atsushi Tanemura, Associate Professor of the Department of Dermatology, Graduate

School of Medicine, Osaka University; Hiroyuki
Murota, Professor of the Department ofDermatology, Nagasaki University Graduate Schoolof Biomedical Sciences; and Ichiro Katayama,
Specially Appointed Professor of the Departmentof Dermatology, Osaka Metropolitan University
Graduate School of Medicine, has elucidated how
sweat gland contractions occur during sweatingin humans.
In this study, the researchers revealed thatconnexins (CXs), which form gap junctions, areabundantly expressed on myoepithelial cells thatplay a critical role in sweat gland contractions
and that these gap junctions are significantly
involved in sweat gland contractions during
sweating (Fig.1). They also showed thatcarbenoxolone (CBX), a gap junction blocker,
inhibited sweat gland activity. Furthermore,they found that GMA, an analogue of CBX,
inhibited both thermogenic (heat-induced) andpsychogenic (emotion-induced) sweating in humans (Figs.2 and 3).
These findings are expected to contribute to the development of next-generation
antiperspirant technologies that go beyond current approaches and to better understanding andtreatment of hyperhidrosis, a sweat gland disorder.
Part of this study was presented at the international conference described below, held fromSeptember 4 to 7, 2023, in Barcelona, Spain, and received the Best Poster Presentation Award.

•Background of the research
Recent global rises in average temperatures have induced excessive sweating not only inindividuals with hyperhidrosis but also in those without this sweating disorder, causing
discomfort and affecting their quality of life (QOL). Antiperspirants are commonly used as aconvenient way to control sweating. They suppress sweating as the active ingredients, aluminumsalts, physically cap the sweat glands. However, according to a survey of antiperspirant users
conducted by Mandom,*4 one in three users is not satisfied with the effectiveness ofantiperspirants, indicating a need for further improvement in antiperspirant functionality.
Toward developing a new antiperspirant technology different from conventional ones, thisresearch group has previously used human sweat glands and demonstrated that sweat is expelled
onto the skin surface by contractions of sweat glands during sweating. However, the detailed
mechanism remained unclear, and no substances had yet been identified that effectively
inhibited sweating.

•Research content

The group collected eccrine sweat glands from human skin tissue, which were then stained andobserved by microscopy. CXs, which form gap junctions, were expressed on myoepithelial cells,
and were involved in sweat gland contractions during sweating. Among the CXs, CX43 was mostabundantly distributed on the myoepithelial cells (Fig.1). CBX,a gap junction blocker,
suppressed both myoepithelial cell movements and sweat gland activity. These results indicatethat gap junctions in myoepithelial cells are a critical factor in sweat gland contraction
during sweating.
Next, they investigated the antiperspirant effect of GMA, an analogue of CBX, on sweating
induced by exercise and mental stress, using a perspiration meter that allows real-timeobservation of sweating behavior. The results showed that GMA applied to the human armpit
delayed the onset of exercise-induced sweating and reduced the total sweat produced by a 15minute exercise (Fig.2). In addition, GMA suppressed the behavior (amplitude) of sweating,suggesting that GMA inhibits sweat gland movements in the human armpit. Furthermore, the local
application of GMA also inhibited palmar sweating induced by the mental stress of a 5-minutemental arithmetic task (Fig.3).

•Impact of this research achievement on society

The new antiperspirant technology found in this research directly targets sweat glands, andthus it could be useful in enhancing the effectiveness of antiperspirants through thedevelopment of antiperspirant products with new functions and products combined withconventional methods. In addition, further elucidation of the dynamic sweating mechanism insweat glands is expected to contribute to a better understanding and treatment of sweatingrelated disease (hyperhidrosis).

•Special notes
This work was presented at the international conference described below, held on September 4

to 7, 2023, in Barcelona, Spain, and won the Best Poster Presentation Award out of 449
presentations (including 76 oral and 373 poster sessions).
The International Federation of Societies of Cosmetic Chemists (IFSCC) 2023
Title:Next-generation antiperspirant technique: Controlling the contraction of human eccrine gland
Presenters:Takeshi Hara, Kie Nakashima, Ayumi Kyuka, Hiroko Kato, Fumitaka Fujita, Atsushi
Tanemura, Yukinobu Nakagawa, Hiroyuki Murota, Ichiro Katayama, and Kiyotoshi Sekiguchi
This research was partly supported by Grants-in-Aid for Scientific Research from the Japan
Society for the Promotion of Science under 17K16337(Elucidation of the contraction mechanismsof human sweat gland in sweating - Improvement the visualization of live sweat gland andAnalysis by using visualization system)and 19K17771(Elucidation of sweat transport mechanisms
in human by visualization of sweat itself in sweat gland).

•Notes and Glossary*1 Connexins
A family of proteins that form gap junctions*2 Gap junctions
Intercellular connections between neighboring cells that allow ions with low watersolubility and electrical signals to pass between cells*3 Monoammonium glycyrrhizate (GMA)
A compound extracted from the herbal medicine licorice root
*4 Survey of antiperspirant users conducted by Mandom.
September 2023/men and women aged 20–59/n=449/Internet survey/survey by Mandom【Message from Takeshi Hara (Manager of Life Science Research Group,
Advanced Technology Institute, Mandom Corporation and Guest Associate
Professor of the Graduate School of Pharmaceutical Sciences, OsakaUniversity)】
Humans can efficiently regulate their body temperature by sweating. It is wellrecognized that this sweating function enables humans to perform exercise for longperiods. However, rising average temperatures due to global warming andpsychosocial stress have increased the opportunities for excessive sweating and thenumber of people suffering from excessive sweating and its associated unpleasantodor. People living with hyperhidrosis, a physical disorder with the primary symptomof excessive sweating, experience difficulties in their daily lives due to thissymptom, resulting in a reduced quality of life (QOL). To address these concerns
about excessive sweating in customers, we have been dedicated to uncovering thesweating mechanism in human sweat glands and developing novel, effective
antiperspirant ingredients. In the future, we intend to implement the findings of ourresearch in real life to improve the QOL of individuals with sweating problems.