Calcineurin/NFATc1 Signaling Links Skin Stem Cell Quiescence to Hormonal Signaling During Pregnancy and Lactation

April 2014 in “ Genes & Development ”

Jill M. Goldstein, Sean A. Fletcher, Eve Roth, Chuansha Wu, Andrew S. Chun, Valerie Horsley

calcineurin Nfatc1 hair follicle stem cell HF SC prolactin receptor Prlr prolactin Jak/Stat5 signaling stem cell quiescence hair growth hormonal signaling pregnancy lactation

Studysummary The researchers reported that in mice, prolactin signaling in the skin epithelium inhibits hair follicle stem cell activation, promoting quiescence during periods of high serum prolactin like pregnancy and lactation. Our plain-language summary of this paper — not a Tressless recommendation.

The study from April 14, 2014, explored how calcineurin/Nfatc1 signaling affects hair follicle stem cell (HF SC) quiescence during pregnancy and lactation in mice. It was found that this signaling pathway regulates the expression of the prolactin receptor (Prlr) and that high serum prolactin levels during pregnancy and lactation activate Prlr, leading to HF SC quiescence through Jak/Stat5 signaling. The study demonstrated that prolactin signaling is crucial for maintaining SC quiescence in the skin, which prevents hair growth during these periods. The research also showed that inhibiting Prl signaling can lead to premature hair regrowth, suggesting that hormonal signals are key in controlling SC activity and hair cycle. The study used various experimental approaches, including genetic and pharmacological manipulations, but the exact number of mice used was not specified.

View this study on genesdev.cshlp.org →

Discuss this study in the Community →

Research cited in this study

25 / 25 results

research The Changes in the Hair Cycle During Gestation and the Post-Partum Period

34 citations , May 2013 in “Journal of the European Academy of Dermatology and Venereology”

In this study, changes in hair cycle phases during pregnancy and the post-partum period showed a rise in telogen rates after delivery, especially among non-breastfeeding women, but no drastic exaggerations were noted.

research Dermal Papilla Cell Number Specifies Hair Size, Shape, and Cycling, and Its Reduction Causes Follicular Decline

211 citations , April 2013 in “Development”

In this study, researchers found that the number of dermal papilla cells in hair follicles determines hair size and shape in mice, suggesting potential avenues for addressing hair loss.

research Age-Associated Inflammation Inhibits Epidermal Stem Cell Function

144 citations , September 2012 in “Genes & development”

This study found that aging in the epidermis disrupts cytokine balance and stem cell function, which may contribute to broader tumor-suppressive mechanisms.

research Live Imaging of Stem Cell and Progeny Behavior in Physiological Hair-Follicle Regeneration

305 citations , June 2012 in “Nature”

This study reports that hair regeneration in live mice involves spatially regulated stem cell divisions and requires mesenchymal interactions, observed in real-time using a novel non-invasive imaging method.

research Hair Loss and Hyperprolactinemia in Women

19 citations , January 2012 in “Dermato-endocrinology”

This study suggests that moderate elevated prolactin levels are unlikely to cause significant hair loss in women, but still warrant further diagnostic investigation to rule out a prolactin-producing pituitary tumor.

research Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling

499 citations , September 2011 in “Cell”

This study found that intradermal adipocyte lineage cells in mice are necessary and sufficient to activate follicular stem cells, highlighting their role in regulating skin stem cell activity.

research Nerve-Derived Sonic Hedgehog Defines a Niche for Hair Follicle Stem Cells Capable of Becoming Epidermal Stem Cells

396 citations , May 2011 in “Cell stem cell”

This study found that Shh from neurons signals to Gli1-expressing cells in the hair follicle, cultivating a niche where these bulge cells can potentially transform into epidermal stem cells in wound healing.

research The Basement Membrane Of Hair Follicle Stem Cells Is A Muscle Cell Niche

294 citations , February 2011 in “Cell”

Nephronectin helps attach muscle cells to hair follicles.

Thyrotropin-Releasing Hormone and Estrogen Differentially Regulate Prolactin and Prolactin Receptor Expression in Female Human Skin and Hair Follicles In Vitro

research Thyrotropin-Releasing Hormone and Estrogen Differentially Regulate Prolactin and Prolactin Receptor Expression in Female Human Skin and Hair Follicles In Vitro

37 citations , March 2010 in “British Journal of Dermatology”

Oestrogen and thyrotropin-releasing hormone affect prolactin and its receptor in human skin and hair, suggesting new treatment options for related conditions.

research Prolactin and the Skin: A Dermatological Perspective on an Ancient Pleiotropic Peptide Hormone

98 citations , December 2008 in “Journal of Investigative Dermatology”

This review discusses the possible impacts of prolactin on skin conditions like psoriasis, alopecia, and stress-related dermatoses, emphasizing the need for further research to explore its therapeutic potential.

research Nfatc1 Balances Quiescence and Proliferation of Skin Stem Cells

415 citations , January 2008 in “Cell”

NFATc1 controls hair stem cell activity, affecting hair growth and could be a target for hair loss treatments.

research Hormonal Regulation of Hair Follicles Exhibits a Biological Paradox

98 citations , February 2007 in “Seminars in Cell & Developmental Biology”

This review explores the hormonal regulation of hair growth and changes with season, age, and sexual development, and calls for improved treatments for hair disorders.

research Prolactin Delays Hair Regrowth in Mice

53 citations , November 2006 in “Journal of Endocrinology”

This study found that prolactin plays a direct role in regulating the timing of hair growth cycles in mice by affecting the skin, rather than through other endocrine factors.

research The Hair Follicle as an Estrogen Target and Source

159 citations , July 2006 in “Endocrine Reviews”

This article discusses the influence of estrogens on hair follicle growth and metabolism, suggesting a significant role alongside androgens in hair growth control but reports no new clinical results.

Human Scalp Hair Follicles Are Both a Target and a Source of Prolactin, Which Serves as an Autocrine and/or Paracrine Promoter of Apoptosis-Driven Hair Follicle Regression

research Human Scalp Hair Follicles Are Both a Target and a Source of Prolactin, Which Serves as an Autocrine and/or Paracrine Promoter of Apoptosis-Driven Hair Follicle Regression

128 citations , March 2006 in “American Journal of Pathology”

The study found that prolactin expressed in human scalp hair follicles acts as an autocrine modulator, inhibiting hair growth and promoting hair follicle regression, which may contribute to hair loss in hyper-prolactinemia patients.

research Molecular Dissection of Mesenchymal–Epithelial Interactions in the Hair Follicle

417 citations , September 2005 in “PLoS biology”

This study developed molecular signatures for dermal papilla cells and their niche, uncovering novel signaling regulators and genes linked to hair disorders, which may inform future hair development research.

Cyclosporin A-Induced Hair Growth in Mice Is Associated with Inhibition of Calcineurin-Dependent Activation of NFAT in Follicular Keratinocytes

research Cyclosporin A-Induced Hair Growth in Mice Is Associated with Inhibition of Calcineurin-Dependent Activation of NFAT in Follicular Keratinocytes

57 citations , June 2003 in “American Journal of Physiology-cell Physiology”

This study found that cyclosporin A treatment enhances hair growth in mice by inhibiting calcineurin-NFAT1 activity, which alters keratinocyte differentiation and apoptosis-related gene expression in hair follicles.

Prolactin and Its Receptor Are Expressed in Murine Hair Follicle Epithelium, Show Hair Cycle-Dependent Expression, and Induce Catagen

research Prolactin and Its Receptor Are Expressed in Murine Hair Follicle Epithelium, Show Hair Cycle-Dependent Expression, and Induce Catagen

91 citations , May 2003 in “American Journal of Pathology”

This study found that prolactin and its receptor are expressed in the murine hair follicle epithelium, influencing hair cycle phases by down-regulating keratinocyte proliferation during anagen and inducing premature catagen.

research Exogen, Shedding Phase of the Hair Growth Cycle: Characterization of a Mouse Model

107 citations , September 2002 in “Journal of Investigative Dermatology”

This study identified a distinct "exogen" phase in the hair cycle during which hair shedding occurs, primarily coupled with the anagen phase, rather than as part of the telogen phase.

Prolactin Signaling Influences the Timing Mechanism of the Hair Follicle: Analysis of Hair Growth Cycles in Prolactin Receptor Knockout Mice

research Prolactin Signaling Influences the Timing Mechanism of the Hair Follicle: Analysis of Hair Growth Cycles in Prolactin Receptor Knockout Mice

14 citations , June 2001 in “Endocrinology”

This study found that disrupting the PRL gene in mice alters the timing of hair cycling events, causing earlier molts and changes in hair characteristics, particularly affecting female mice more significantly.

research Prolactin Signaling Influences the Timing Mechanism of the Hair Follicle: Analysis of Hair Growth Cycles in Prolactin Receptor Knockout Mice

73 citations , June 2001 in “Endocrinology”

In this study, researchers found that disrupting the PRL gene in mice led to earlier hair molting, especially in females, suggesting that PRL inhibits murine hair cycle events.

research An Estrogen Receptor Pathway Regulates the Telogen-Anagen Hair Follicle Transition and Influences Epidermal Cell Proliferation

154 citations , October 1996 in “Proceedings of the National Academy of Sciences of the United States of America”

This study found that 17-beta-estradiol inhibits hair growth in mice by blocking hair follicles in the telogen phase, whereas an estrogen receptor antagonist promotes hair growth by initiating anagen.

research The Localization and Characterization of Insulin-Like Growth Factor-I Receptors and the Investigation of Melatonin Receptors on the Hair Follicles of Seasonal and Non-Seasonal Fiber-Producing Goats

26 citations , October 1996 in “Journal of Endocrinology/Journal of endocrinology”

This study concluded that IGF-I receptors are present on hair follicles and sebaceous glands of cashmere and Angora goats, but melatonin receptors are absent.

research Disorder of Hair Growth in Hyperprolactinemia

3 citations , January 1988 in “PubMed”

This study observed that functional hyperprolactinemia in several women was associated with skin symptoms such as seborrhea, acne, and hair-related issues, resembling androgen-induced conditions.

research Study of Postpartum Alopecia

24 citations , May 1963 in “Archives of Dermatology”

In this study of postpartum alopecia, most patients experienced significant hair regrowth within four to six months, and heredity did not appear to be a significant factor in hair loss.