How is sebum secretion regulated?

Question

The principle of homeostasis in biology says that living organisms try to maintain some sort of equilibrium. Doing that requires the use of feedback mechanisms to regulate things like temperature, salinity, etc. Are there any feedback mechanisms the body uses to regulate the output of the skin's sebaceous glands? If so, what are they, and on what timescale do they operate?

Answer 1

Nice question! Unfortunately, the complete list of pathways involved in regulation of sebum production and secretion rate by sebaceous glands are not understood yet (Picardo et al, 2009). However, we know that sebum production is continuous and is not regulated by neural mechanisms (Thiboutot et al, 2004). Retinoids, hormones, and growth factors are known to influence sebaceous gland growth and differentiation (Zouboulis et al, 1998). Also, androgens and growth hormones are known to promote sebaceous gland differentiation (Deplewski et al, 1999, Rosenfield et al, 1998) whereas estrogens and retinoids, like 13-cis retinoic acid, inhibit their differentiation (Strauss et al, 1962).

In retinoids, isoretinoin is shown to have greater sebosuppressive action as compared to all-trans or 9-cis retinoic acid (Hommel et al, 1996). In androgens, androgen receptors have been localized to the basal layer of the sebaceous gland and the outer root sheath keratinocytes of the hair follicle, and testosterone and dihydrotestosterone are the major androgens that interact with these receptors (Liang et al, 1993). However, the molecular mechanisms through which androgens interact with these receptors and sebaceous glands are not understood yet (Thiboutot et al, 2004). Apart from this, insulin and Insulin-like Growth Factor 1 (IGF-1) also play a critical role here. Acne is considered as IGF-1 mediated disease, and high levels of sugar (caused due to diet) induce high levels of insulin and IGF-1. Both these hormones amplify the stimulatory effect of GH on sebocytes and augment mitogenic downstream signalling pathways of insulin receptors, IGF-1 receptor and fibroblast growth factor receptor-2b (Melnik et al, 2009).

Other (known) substances which are found to regulate sebum secretion include histamine (due to presence of H-1 receptor on sebocytes, Pelle et al, 2008), LXR ligands (due to presence of Liver X Receptor, Zouboulis et al, 2009), PPAR ligands (due to presence of Peroxisome Proliferator-Activated Receptor, Trivedi et al, 2006), vitamin D deficiency (Yildizgören et al, 2014), neuropeptides (Ganceviciene et al, 2009), etc. See the image below (from Makrantonaki et al, 2011) for visual representation:

In spite of this, elucidating the mechanism of regulation of sebum secretion by sebaceous glands is a difficult task since, although evidence suggests that nonendocrine factors may also be an important part for regulation along with endocrine factors, the nature of this secretion and the regulation of the secretory process seem to differ among the various types of glands which, in spite of being similar in structure, might be different in function and regulation (Thody et al, 1989).

References:

_{1. Picardo, Mauro et al. “Sebaceous Gland Lipids.” Dermato-endocrinology 1.2 (2009): 68–71. Print.}

_{2. Diane Thiboutot, Regulation of Human Sebaceous Glands, Journal of Investigative Dermatology, Volume 123, Issue 1, July 2004, Pages 1-12, ISSN 0022-202X, http://doi.org/10.1111/j.1523-1747.2004.t01-2-.x.}

_{3. C.C. Zouboulis, L. Xia, H. Akamatsu, H. Seltmann, M. Fritsch, S. Hornemann, R. Ruhl, W. Chen, H. Nau, C.E. Orfanos The human sebocyte culture model provides new insights into development and management of seborrhoea and acne Dermatology., Volume 196, Issue 1, 1998, pp. 21–31}

_{4. D. Deplewski, R.L. Rosenfield Growth hormone and insulin-like growth factors have different effects on sebaceous cell growth and differentiation Endocrinology., Volume 140, Issue 9, 1999, pp. 4089–4094}

_{5. R.L. Rosenfield, D. Deplewski, A. Kentsis, N. Ciletti Mechanisms of androgen induction of sebocyte differentiation Dermatology., Volume 196, Issue 1, 1998, pp. 43–46}

_{6. J.S. Strauss, A.M. Kligman, P.E. Pochi The Effect of Androgens and Estrogens on Human Sebaceous Glands J Invest Dermatol., Volume 39, 1962, pp. 139–155}

_{7. L. Hommel, J.M. Geiger, M. Harms, J.H. Saurat Sebum excretion rate in subjects treated with oral all-trans-retinoic acid Dermatology., Volume 193, Issue 2, 1996, pp. 127–130}

_{8. T. Liang, S. Hoyer, R. Yu Immunocytochemical localization of androgen receptors in human skin using monoclonal antibodies against the androgen receptor J Invest Dermatol., Volume 100, 1993, pp. 663–666}

_{9. Melnik BC, Schmitz G. Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Exp Dermatol. 2009;18:833–841}

_{10. Edward Pelle, James McCarthy, Holger Seltmann, Xi Huang, Thomas Mammone, Christos C. Zouboulis, Daniel Maes, Identification of Histamine Receptors and Reduction of Squalene Levels by an Antihistamine in Sebocytes, Journal of Investigative Dermatology, Volume 128, Issue 5, May 2008, Pages 1280-1285, ISSN 0022-202X, http://doi.org/10.1038/sj.jid.5701160}

_{11. Zouboulis, Christos C. “Sebaceous Gland Receptors.” Dermato-endocrinology 1.2 (2009): 77–80. Print.}

_{12. Nishit R. Trivedi, Zhaoyuan Cong, Amanda M. Nelson, Adam J. Albert, Lorraine L. Rosamilia, Surendra Sivarajah, Kathryn L. Gilliland, Wenlei Liu, David T. Mauger, Robert A. Gabbay, Diane M. Thiboutot, Peroxisome Proliferator-Activated Receptors Increase Human Sebum Production, Journal of Investigative Dermatology, Volume 126, Issue 9, September 2006, Pages 2002-2009, ISSN 0022-202X, http://doi.org/10.1038/sj.jid.5700336}

_{13. Yildizgören, Mustafa Turgut, and Arzu Karatas Togral. “Preliminary Evidence for Vitamin D Deficiency in Nodulocystic Acne.” Dermato-endocrinology 6.1 (2014): e983687. PMC. Web. 23 Apr. 2017.}

_{14. Ganceviciene, Ruta et al. “The Role of Neuropeptides in the Multifactorial Pathogenesis of Acne Vulgaris.” Dermato-endocrinology 1.3 (2009): 170–176. Print.}

_{15. Makrantonaki, Evgenia, Ruta Ganceviciene, and Christos Zouboulis. “An Update on the Role of the Sebaceous Gland in the Pathogenesis of Acne.” Dermato-endocrinology 3.1 (2011): 41–49. PMC. Web. 23 Apr. 2017.}

_{16. Thody, A. J. & Shuster, S. Control and function of sebaceous glands. Physiol Rev 69, 383–416 (1989)}