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 sex...
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| Veröffentlicht in: | The FASEB journal 2020-08, Vol.34 (8), p.10887-10906 |
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| creator | Mohandass, Adithya Krishnan, Vivek Gribkova, Ekaterina D. Asuthkar, Swapna Baskaran, Padmamalini Nersesyan, Yelena Hussain, Zahir Wise, Leslie M. George, Robert E. Stokes, Nadarra Alexander, Brenda M. Cohen, Alejandro M. Pavlov, Evgeny V. Llano, Daniel A. Zhu, Michael X. Thyagarajan, Baskaran Zakharian, Eleonora |
| description | 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. |
| doi_str_mv | 10.1096/fj.202000794R |
| format | Article |
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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.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.202000794R</identifier><identifier>PMID: 32609392</identifier><language>eng</language><publisher>United States: John Wiley and Sons Inc</publisher><subject>aggression ; Aggression - physiology ; Animals ; Behavior, Animal - physiology ; dopaminergic neurons ; Dopaminergic Neurons - metabolism ; Dopaminergic Neurons - physiology ; Female ; Male ; Mice ; Receptors, Androgen - metabolism ; reward system ; Sex Characteristics ; sexual Behavior ; Sexual Behavior, Animal - physiology ; Signal Transduction - physiology ; Social Behavior ; testosterone ; Testosterone - metabolism ; transient receptor potential melastatin 8 (TRPM8) channel ; TRPM Cation Channels - metabolism ; Ventral Tegmental Area - metabolism ; Ventral Tegmental Area - physiology</subject><ispartof>The FASEB journal, 2020-08, Vol.34 (8), p.10887-10906</ispartof><rights>2020 The Authors. published by Wiley Periodicals LLC on behalf Federation of American Societies for Experimental Biology</rights><rights>2020 The Authors. 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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.</description><subject>aggression</subject><subject>Aggression - physiology</subject><subject>Animals</subject><subject>Behavior, Animal - physiology</subject><subject>dopaminergic neurons</subject><subject>Dopaminergic Neurons - metabolism</subject><subject>Dopaminergic Neurons - physiology</subject><subject>Female</subject><subject>Male</subject><subject>Mice</subject><subject>Receptors, Androgen - metabolism</subject><subject>reward system</subject><subject>Sex Characteristics</subject><subject>sexual Behavior</subject><subject>Sexual Behavior, Animal - physiology</subject><subject>Signal Transduction - physiology</subject><subject>Social Behavior</subject><subject>testosterone</subject><subject>Testosterone - metabolism</subject><subject>transient receptor potential melastatin 8 (TRPM8) channel</subject><subject>TRPM Cation Channels - metabolism</subject><subject>Ventral Tegmental Area - metabolism</subject><subject>Ventral Tegmental Area - physiology</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp9kcFvFSEQxonR2Gf16NVw9LItsCwLHkxsY22TGk2tZ8KD4T1eWFhht9r4z7v6atWLp5nM_OabyXwIPafkiBIljv3uiBFGCOkVv3qAVrRrSSOkIA_RikjFGiFaeYCe1LpbIEqoeIwOWiaIahVboe_XVx_fS2wqnraAixmDwxPUKdcJSk6Aa9gkE0Pa4AIWximXV_hiGGOwZgo5VRzSfhQ2c_xVwtljF4Zcxm2wuMK32URsksM127Cka9iam5BLfYoeeRMrPLuLh-jz2dvr0_Pm8sO7i9M3l43lSorGeec4WLP2VllhhCOC9MzwVnaWcbl0pO9d1wLz4G0HyrZEOOr98hVJKbSH6PVed5zXAzgLaSom6rGEwZRbnU3Q_3ZS2OpNvtE9V0LQfhF4eSdQ8pd5-Y4eQrUQo0mQ56oZp4pTqvpuQZs9akuutYC_X0OJ_mmY9jv9x7CFf_H3bff0b4cWgO-BryHC7f_V9NmnE8ZIz0X7AxhDpRM</recordid><startdate>202008</startdate><enddate>202008</enddate><creator>Mohandass, Adithya</creator><creator>Krishnan, Vivek</creator><creator>Gribkova, Ekaterina D.</creator><creator>Asuthkar, Swapna</creator><creator>Baskaran, Padmamalini</creator><creator>Nersesyan, Yelena</creator><creator>Hussain, Zahir</creator><creator>Wise, Leslie M.</creator><creator>George, Robert E.</creator><creator>Stokes, Nadarra</creator><creator>Alexander, Brenda M.</creator><creator>Cohen, Alejandro M.</creator><creator>Pavlov, Evgeny V.</creator><creator>Llano, Daniel A.</creator><creator>Zhu, Michael X.</creator><creator>Thyagarajan, Baskaran</creator><creator>Zakharian, Eleonora</creator><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>202008</creationdate><title>TRPM8 as the rapid testosterone signaling receptor: Implications in the regulation of dimorphic sexual and social behaviors</title><author>Mohandass, Adithya ; 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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.</abstract><cop>United States</cop><pub>John Wiley and Sons Inc</pub><pmid>32609392</pmid><doi>10.1096/fj.202000794R</doi><tpages>20</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | aggression Aggression - physiology Animals Behavior, Animal - physiology dopaminergic neurons Dopaminergic Neurons - metabolism Dopaminergic Neurons - physiology Female Male Mice Receptors, Androgen - metabolism reward system Sex Characteristics sexual Behavior Sexual Behavior, Animal - physiology Signal Transduction - physiology Social Behavior testosterone Testosterone - metabolism transient receptor potential melastatin 8 (TRPM8) channel TRPM Cation Channels - metabolism Ventral Tegmental Area - metabolism Ventral Tegmental Area - physiology |
| title | TRPM8 as the rapid testosterone signaling receptor: Implications in the regulation of dimorphic sexual and social behaviors |
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