Anatomy of sebaceous glands

1. Anatomy and Physiology of the
Sebaceous Glands
BY DR MAYURI B M

2. Introduction

3. Embryology
Period of
Gestation
Embryological development
3 weeks Epidermis single layered
4 weeks Epidermis becomes double layered
10-12 weeks First germ cells of the future folliculo-sebaceous– Apocrine units are observed
13weeks Three buds are observed – future representation
Apocrine gland - top
Sebaceous gland - middle
Arrector pili muscle of the hair follicle - bottom.
13-15 weeks Follicles extend downward into the dermis, rudiments of the sebaceous glands
appear on the posterior surfaces of the hair pegs.
Epidermal stem cells at bulge via signalling pathways – undergo differentiation to form full
mature and well differentiated sebocytes

4. Epidermal stem
cells at bulge –
undergo
differentiation

5. 17 week • Formation of solid cord around the acini of the sebaceous gland
• Cells composing the cord are filled with sebum lose integrity -> rupture and form
a channel that establishes first pilosebaceous canal
III trimester Glands are highly active
Later functional throughout foetal life
At birth Sebum forms part of the vernix caseosa
Activity of sebaceous glands continues for a few months in postnatal life under
influence maternal androgens.
At end of 1 year Activity declines and remains low until puberty
At puberty Activity increases under the influence of its own androgens, 5α-dihydrotestesterone
(DHT).

6. Formation of
Solid cord
First
pilosebaceous
canal

7. 1
2

8. Signaling pathways and transcription factors
in cell lineage determinations
Gain of function
mutation –Increases
number and size of
sebocytes
Loss of function
mutation –normal
sebocyte
differentiation
Sonic hedgehog (Shh) and Wnt or wingless (Wnt) signaling pathways are intricately
involved in embryonic patterning and cell fate decisions.
Stimulation –hair
follicle
differentiation
Inhibition via
Lef1-beta catenin
causes sebocyte
differentiation
Shh Wnt

9. • Lef1: lymphoid enhancer binding factor 1
• Myc: myelocytomatosis oncogene
• Shh :Sonic hedgehog
• Wnt, wingless (wg)/int

10. Differentiation of sebocytes
Undifferentiated
(basal)
small cells with a high NC ratio.
Early differentiated larger cells with a decreased NC ratio
Advanced differentiated Increase in cell size and decreased NC
ratio. Multiple cytoplasmic lipid droplets
are distributed inside the cytoplasm.
Fully differentiated Abundant, partially large, cytoplasmic
lipid droplets.
Mature A disorganized large cell with denatured
nucelei; the lack of cytoplasmic lipids is
caused by lysis of the
cell blood cell membrane.

11. Genes and their proteins involved in
sebaceous differentiation and maturation

12. Anatomy
• Keratinized follicular infundibulum
Acro-infundibulum : keratinization and granular layer
 Infra-infundibulum : Tricholemmal keratinization and
absent granular layer
• Hair Shaft
• Sebaceous gland
• Sebaceous duct connects the gland with infundibulum

13. Distribution
• Present over the entire body surface, except palms and
soles.
• face and scalp 400-900 sebaceous glands per cm2.
• Skin of the trunk and extremities 100 sebaceous glands
per cm2.
• Most abundant and metabolically more active on face and
scalp.

14. • Few - back of hands and feet.
• Numerous - scalp, face, external auditory meatus, mid chest, back, and
anogenital surface.
• Ectopic sebaceous glands : mucous membranes, mucocutaneous
junctions.

15. Types of sebaceous glands
Sebaceous duct Open directly in the epidermis : Free sebaceous gland
Open into hair follicle : 3 types

17. Modified Sebaceous Glands
Eyelids
 Vellus hair follicles of the skin of the
eyelids.
 Hair follicles of the eyelashes : glands of
Zeis.
 Present within tarsus : Meibomian glands

18. • Tyson’s glands of prepuce
• Free sebaceous glands on the mucocutaneous surfaces of
female genitalia
• Montgomery’s tubercles on areola of nipples
• Ectopic glands in cervix uteri, tongue, and parotid glands
• Margins of lip (Fordyce’s spots)

19. Histology
Lobules of a mature sebaceous gland –
 Peripheral or basal germinative cells
Number -single layer
Shape - fusiform or flattened cells
Nucleus - hyperchromatic
Cytoplasm - scanty

20. • Following layers as the cells differentiate towards the center
- Cells Size  increases
- cytoplasm pale and vacuolated
- Nucleus and other organelles  pushed terminally, become distorted and disintegrated
- Lipid accumulation
• Gland is surrounded  adventitial dermis with fibrillary collagen
 abundant vascular substance
 ground substance.

21. Sebaceous duct
 Lined by a stratified squamous epithelium which
shows gradual keratinization.

22. Corneal layer is in the form of a
slightly eosinophilic cuticle.
The cuticle of the sebolemma : serrated
or spiculated contour, with their spicules
protruding towards the lumen of the
duct

23. Electron microscopy
• Undifferentiated cells at the periphery of the glands rest
upon a basement membrane , are connected to each other
by desmosomes.
• Cells –tonofilaments
-abundant smooth endoplasmic reticulum (SER)
-Golgi apparatus
- many mitochondria
• The lipid droplets arise in SER and Golgi apparatus

24. Immunocytochemical studies
• Steroid receptor : Androgen receptors present over gland and duct.
• Nonsteroidal receptor :
- Peroxisome proliferators activated receptors (PPARs) – 3 subtypes (alpha , beta , gama )
- PPAR alpha-1 gene : ductal cells of normal skin as well as in comedones
• Sebocytes express melanocortin (MC)-1 receptors and are target cells for alpha
melanocyte stimulating hormone (alpha-MSH).

25. Sebum production
• The sebaceous glands exude lipids by disintegration of
entire cells, a process known as holocrine secretion.
• A multistep cell-specific lysosomal DNAse2-mediated
mode of programmed cell death .
• 7.4 days  formation of the cell to its rupture.

26. Sebocyte turnover time 14 days
Flow of sebum Relatively continuous
Average rate of sebum
production
1 mg/10 cm2 every 3 hours
Color Light yellow
Consistency Viscous fluid
Composition
P.acnes P.granulosum
esterase (acro-infundibulum)
Wax esters (26%) and Squalene (12%)
Cholesteryl esters (3%) and Cholesterol (1.5%)
Acyl
glycerol
free fatty
acids
(57.5%)

27. Factors regulating sebaceous gland size and
sebum production
• Increasing age  size of sebaceous glands increases
 Number remains same
• Avg size : 0.2 mm2 ± 0.5 mm2 to 0.4 mm2 ± 2.1 mm2.
• The sebaceous cells of prepubertal, hypogonadal boys, men are qualitatively similar to
those of normal adults, even though the glands are smaller
• Turnover rate in older adults is slowed down compared with young adults.

28. Hormonal Regulation of sebaceous glands
Sebaceous gland component Actions in sebaceous glands
A – Hypothalamic–pituitary–adrenal(-like) and other hormonal axes
• Corticotropin-releasing hormone ↑ lipid and androgen synthesis
↑ production of IL-6, IL-8 (CRH-R2)
• α-Melanocyte stimulating hormone ↑ sebocyte differentiation
lipid synthesis
• Growth hormone
• insulin-like growth factor-1
↑ sebocyte proliferation
↑ lipid and androgen synthesis

29. C – Androgens
• Testosterone
• dihydrotestosterone (DHT)
↑ sebocyte proliferation/differentiation
lipid synthesis (especially DHT)
May ↑ infundibular keratinization
D – OTHERS
• Peroxisome proliferator-activated
receptors (PPAR α, PPAR γ >
PPAR β )
↑ Lipogenesis, prostaglandin E2
release, IL-6 release,
COX2 synthesis
B – Other neuropeptides
Substance P ↑ sebocyte proliferation/differentiation
↑ production of inflammatory
cytokines

30. Androgens
• Exogenous androgens  do not stimulate sebaceous glands
• Endogenous androgens  stimulates sebaceous glands
• Genetic deficiency of androgen receptors  no detectable sebum secretion
Newborns 2- 4 year-old
children
adrenarche, puberty adulthood
Dehydroepiadrosterone
sulfate
high very low rise peaks Men >
women
declines
Sebum Secretion High Very low Rise peaks Men
slightly
higher
Declines

32. Estrogen
• Decreases size of sebaceous glands
• Reduces sebum production
• At higher doses by reducing endogenous androgen production through the pituitary–
gonadal axis.
Progesterone
• At physiological doses has no effect on sebaceous glands

33. Adrenocorticotropic hormone (ACTH)
• Hyperplasia of sebaceous glands
• Increases sebum production
• Increases mitosis of the sebaceous cells
Pituitary hormones
• Act directly on sebaceous glands or indirectly via endocrine glands that they control
• These may act independently or synergistically with other hormones.

35. Functions of sebaceous glands
Embryology ,
Development,
and
Differentiation
3-D organization of skin surface lipids
Maintains integrity of the skin barrier
Influence on follicular differentiation
Highly complex acetylcholine receptor
expression pattern

36. Synthetic
Activity
Production of vernix caseosa
Production of sebum
Histamine-1 receptor expression
Inhibition of squalene synthesis by antihistamines
Protection Natural photoprotective activity against ultraviolet B irradiation
Thermoregulatory and repelling properties
Involved in wound healing
Transportation Delivery of antioxidants to and from the skin surface
Sebum as vehicle of fragrance

37. Inflammation
and
Immunity
Production of proinflammatory and of anti inflammatory lipids
Toll-like receptor 2–induced upregulation of lipogenesis
• Antimicrobial peptides – Cathelicidin , psoriasin, beta-
defensin 1, and - defensin 2
• proinflammatory cytokines and chemokines
• ectopeptidases
Cathelicidin - antimicrobial activity against Propionibacterium
acnes
Contributes to skin inflammation -promotes differentiation :Th17
lymphocytes
Role in pathogen recognition and protection of the skin surface

38. Expression of vitamin D receptor
vitamin D–metabolizing enzymes
Expression of retinoid-metabolizing cytochrome P450 enzymes
Modification of lipid synthesis by combined androgens ,PPAR-
ligands, estrogens ,IGF-1 and IGF-1 complex
Exhibition and affection by a regulatory neuropeptide program
Endocrine
Properties
Regulates endocrine function of the skin
Regulation of local androgen synthesis
Substantial involvement in the hormonally induced skin aging
process

39. Conclusion
• The regulation of sebaceous glands and human sebum production is complex.
• Advances are being made in this area, which may lead to alternative therapies for
the reduction of sebum and improvements in acne.

40. REFERENCES
• Pochi PE .Sebum :Its nature and physiopathologic responses. In: Moschella SL,
Hurley JE , editor.Moschella and Hurley's dermatology 4 th ed. New Delhi ;
London: Jaypee Brothers; 2020. p. 75–7.
• Zouboulis CC.Skin glands : Sebaceous glands , Eccrine glands and Apocrine
glands . In: Kang S, editor . Fitzpatrick's dermatology 9 th ed. New York:
McGraw-Hill Education; 2019. p. 70–89.
• Schaller M. Structure and function of eccrine , apocrine and sebaceous glands . In:
Bolognia, Schaffer, Cerroni, Callen,editor. Dermatology 4 th ed. London: Elsevier;
2018. p. 583–6.

41. • M. GCE, et al. Structure and function of skin In: Rook AJ, Barker J, Bleiker T, Chalmers
R, Creamer D. Rook's Textbook of Dermatology. 9 th. Chichester, West Sussex (UK):
Wiley Blackwell; 2016. p. 2.8–.9.
• Storm CA, Seykora JT. Cutaneous adnexal neoplasms. Am J Clin Pathol. 2002 ;118 p
:755-76.
• HIBBS RG. Electron microscopy of human axillary sebaceous glands. J Invest Dermatol.
1962;38:329-36.
• F. Labrie, V. Luu-The, C. Labrie, G. Pelletier, and M. El-Alfy . Intracrinology and the
skin .2000, Hormone Res, 54, p. 219.