Polymorphism of Extrapituitary Promoter of PRL Gene and Relationships With Serum Prolactin Levels in Acne Vulgaris.

Acne Vulgaris Clinical Trial

Official title:

Polymorphism of Extrapituitary Promoter of PRL Gene and Relationships With Serum Prolactin Levels in Acne Vulgaris.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03186222
• Other study ID #: POEPOPRGAGARWSPLIAV
• Status: Not yet recruiting
• Phase: N/A
• First received: June 11, 2017
• Last updated: June 12, 2017
• Start date: January 2018
• Est. completion date: June 2019

Study information

• Verified date: June 2017
• Source: Assiut University
• Contact: Sara Awad, MD
• Phone: +201023102094
• Email: saramawad[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Acne vulgaris is one of the most common skin diseases. It is a disease of the pilosebaceous units, clinically characterized by seborrhea, comedones, papules, pustules, nodules and, in some cases, scarring.

Description:

The pathogenesis of acne has been attributed to multiple factors such as increased sebum production, alteration of the quality of sebum lipids, regulation of cutaneous steroidogenesis, androgen activity, interaction with neuropeptides, exhibition of pro- and anti- inflammatory properties, follicular hyperkeratinization and the action of Propionibacterium acnes (P. acnes) within the follicle .

Central or peripheral stress may induce the development of clinical inflammation in the pilosebaceous unit, leading to the development of acne lesions or to exacerbation of pre-existing acne . Prolactin is one of the major hormonal signals that are immediately upregulated on psychoemotional and physical stress .

The discovery of locally produced extrapituitary prolactin and that human skin is both a source and target of prolactin production has increased interest in cutaneous prolactin research . Prolactin and prolactin receptors expression have now been demonstrated in several cutaneous cell populations, including keratinocytes, fibroblasts, sweat glands and sebaceous glands. Hence, prolactin is likely to be involved as a mediator in the ''brain-skin axis'' .

Given that the mammary gland is an epidermal derivative, it is not surprising that the pilosebaceous unit, another epidermal derivative, has also surfaced as a prominent, non-classical prolactin target organ expressing prolactin receptors .

In human skin, Prolactin and prolactin receptors are both expressed in the sebaceous gland , and prolactin stimulates sebum production . These effects are evident in women with hyperprolactinemia, who develop hirsutism and seborrhea, not uncommonly associated with female pattern balding . Patients treated with hyperprolactinemia-inducing neuroleptic agents also develop seborrhea . As sebocytes are prominent target cells of neuroendocrine signaling , prolactin might also contribute to the aggravating effect of psychoemotional stress on acne vulgaris. Besides the stimulation of sebocyte proliferation, which enhances holocrine secretion of this gland, this might also be related to effects on peripheral androgen metabolism .

The secretion of extrapituitary prolactin is regulated by the alternative promoter of prolactin gene , and the G/T polymorphism in position -1149 seems to be associated with level of prolactin expression .

In view of the recognized increase of human prolactin serum levels upon psychoemotional stress and the exacerbating effect of psychological stress on acne, together with a proposed role of prolactin in acne pathogenesis, it would be interesting to investigate the role of prolactin in acne vulgaris

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: June 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 40 Years

Eligibility

Inclusion Criteria: patients with acne vulgaris.

Exclusion Criteria:

• patients below 12 years of age

• patients recieving disorders and drug that could alter levels of prolactin such as thyroid disorders, renal and/or hepatic failure and drug use.

Related Conditions & MeSH terms

• Acne Vulgaris

Intervention

Diagnostic Test:
• blood sample
Serum PRL levels are measured using ELISA assay kit in both groups and correlated with severity of acne in acne group. The genomic DNA from peripheral leukocytes is extracted. Genotyping of 1149G/T single nucleotide polymorphism (SNP) PRL extrapituitary promoter is done in acne patients and healthy individuals (control group) using PCR-RFLP method.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (8)

Arck PC, Slominski A, Theoharides TC, Peters EM, Paus R. Neuroimmunology of stress: skin takes center stage. J Invest Dermatol. 2006 Aug;126(8):1697-704. Review. — View Citation

Ganceviciene R, Graziene V, Böhm M, Zouboulis CC. Increased in situ expression of melanocortin-1 receptor in sebaceous glands of lesional skin of patients with acne vulgaris. Exp Dermatol. 2007 Jul;16(7):547-52. — View Citation

Langan EA, Ramot Y, Goffin V, Griffiths CE, Foitzik K, Paus R. Mind the (gender) gap: does prolactin exert gender and/or site-specific effects on the human hair follicle? J Invest Dermatol. 2010 Mar;130(3):886-91. doi: 10.1038/jid.2009.340. Epub 2009 Nov 5. — View Citation

Oakes SR, Rogers RL, Naylor MJ, Ormandy CJ. Prolactin regulation of mammary gland development. J Mammary Gland Biol Neoplasia. 2008 Mar;13(1):13-28. doi: 10.1007/s10911-008-9069-5. Epub 2008 Jan 25. Review. — View Citation

Paus R. Does prolactin play a role in skin biology and pathology? Med Hypotheses. 1991 Sep;36(1):33-42. — View Citation

Reem GH, Ray DW, Davis JR. The human prolactin gene upstream promoter is regulated in lymphoid cells by activators of T-cells and by cAMP. J Mol Endocrinol. 1999 Jun;22(3):285-92. — View Citation

Zouboulis CC, Eady A, Philpott M, Goldsmith LA, Orfanos C, Cunliffe WC, Rosenfield R. What is the pathogenesis of acne? Exp Dermatol. 2005 Feb;14(2):143-52. — View Citation

Zouboulis CC, Schagen S, Alestas T. The sebocyte culture: a model to study the pathophysiology of the sebaceous gland in sebostasis, seborrhoea and acne. Arch Dermatol Res. 2008 Sep;300(8):397-413. doi: 10.1007/s00403-008-0879-5. Epub 2008 Aug 9. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	polymorphism of extrapituitary promoter of PRL gene in acne cases and controls	The blood samples are taken in the morning hours, between 08:00 and 10:00 am The genomic DNA from peripheral leukocytes is extracted. Genotyping of 1149G/T single nucleotide polymorphism (SNP) PRL extrapituitary promoter is done in acne patients and healthy individuals (control group) using PCR-RFLP method.; The genomic DNA from peripheral leukocytes is extracted. Genotyping of 1149G/T single nucleotide polymorphism (SNP) PRL extrapituitary promoter is done in acne patients and healthy individuals (control group) using PCR-RFLP method.	1 year
Secondary	serum prolactin levels in acne patients and controls and among different acne severity grades	The blood samples are taken in the morning hours, between 08:00 and 10:00 am. Serum PRL levels are measured using ELISA assay kit in both groups and correlated with severity of acne in acne group.	1 year