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ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 1  |  Page : 253-256

Role of insulin-like growth factor-1 receptor in female androgenetic alopecia


Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission29-May-2018
Date of Decision19-Jun-2018
Date of Acceptance24-Jun-2018
Date of Web Publication25-Mar-2020

Correspondence Address:
Sabreen A.A. Elsherif
Elshohada, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_185_18

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  Abstract 

Objectives
To find if there is a role of insulin-like growth factor-1 receptor (IGF-1R) in female androgenetic alopecia (FAGA).
Background
Patterned hair loss continues to be one of the most important hair problems affecting both men and women. It is the most common form of alopecia, affecting up to 50% of women in the course of their lives. Insulin-like growth factor-1 (IGF-1) is one of the most potent natural activators of the protein kinase B signaling pathway, a stimulator of cell growth and proliferation, and a potent inhibitor of programed cell death. IGF-1 is a physiological regulator of hair growth cycle. It helps maintain the anagen stage.
Patients and methods
This case–control study was conducted on 20 FAGA patients and 10 age-matched healthy female patients with no androgenetic alopecia as control. They were chosen from Dermatology Clinic at Menoufia University Hospital between April 2017 to April 2018.They were subjected to history taking and complete medical examination. Punch biopsies were taken, and by immunohistochemical staining, the degree of intensity and the percentage of IGF-1R were determined.
Results
The degree of intensity and percentage of IGF-1R in the diseased patients showed statistically significant difference from the normal patients (P = 0.001). There was no significant correlation between IGF-1R expression and age (P = 0.120) and menstrual history (P = 0.189), respectively.
Conclusion
On the basis of the results, it could be concluded that IGF-1R markedly diminished in FAGA.

Keywords: androgenetic alopecia, activator of protein kinase signaling pathway, female androgenetic alopecia, insulin -like growth factor-1, insulin-like growth factor-1receptors, patterned hair loss


How to cite this article:
Hamam MA, Yasien HA, Mahmoud SF, Elsherif SA. Role of insulin-like growth factor-1 receptor in female androgenetic alopecia. Menoufia Med J 2020;33:253-6

How to cite this URL:
Hamam MA, Yasien HA, Mahmoud SF, Elsherif SA. Role of insulin-like growth factor-1 receptor in female androgenetic alopecia. Menoufia Med J [serial online] 2020 [cited 2020 Mar 30];33:253-6. Available from: http://www.mmj.eg.net/text.asp?2020/33/1/253/281267




  Introduction Top


Female pattern hair loss (FPHL) is characterized by progressive hair loss, especially of scalp hair, and has distinctive patterns of loss in women versus men, but in both genders the central scalp is the most severely affected[1],[2],[3]. It often begins around puberty and is known to affect the self-esteem and the individual's quality of life[4]. It is a common cause of hair loss in women characterized by diffuse reduction in hair density over the crown and frontal scalp with retention of the frontal hairline[5]. Patterned hair loss commencing in the adolescent period leads to a well-established bald appearance before 30 years of age and is called adolescent androgenetic alopecia (AGA) or premature AGA or early onset AGA[6]. Male pattern baldness develops in 30–100% of men with increasing age from 17 to 80 years[7]. New emergent therapies like topical androgens, prostaglandins, latanoprost, antibiotics and antifungal, growth factors, stem cell therapies, scalp micro-needling, and platelet-rich plasma therapy are available and practiced off-label[7],[8],[9]. Hair transplantation and low-level laser light are the other options available with varied treatment efficacy and only recommended for patients whose medication regimen has failed[10],[11]. Regardless of which medication is utilized, the response is slow, and requires patience and persistence in both patients and clinicians[12]. So, searching for new therapies for AGA and improving the effectiveness of existing ones, therefore are of utmost importance. Insulin-like growth factor-1 (IGF-1) is a physiological regulator of hair growth cycle. IGF-1 helps maintain the anagen stage. In addition, some hair loss treatments may exert their therapeutic effects via IGF-1. Theoretically, treatments that can stimulate the secretion of IGF-1 may slow hair loss. IGF-1 is one of the major regulators of cellular proliferation and differentiation[13].

The aim of this study is to find if insulin-like growth factor-1 receptor (IGF-1R) can be helpful in treating female androgenetic alopecia (FAGA).


  Patients and Methods Top


This case–control study was conducted on 20 FAGA patients and 10 age-matched healthy females with no AGA as control. The cases were chosen randomly from Dermatology Clinic at Menoufia University Hospital. We obtained a written consent form approved by the Ethical Committee of Menoufia Faculty of Medicine from each participant, before the study initiation. This study will be aided by Pathology Department at Menoufia Faculty of Medicine. We relied on the patient's history and the typical clinical presentation of FPHL, which is characterized by progressive hair loss, especially of scalp hair, and has distinctive patterns of loss in women versus men, but in both genders the central scalp is the most severely affected. It is characterized by diffuse reduction in hair density over the crown and frontal scalp with retention of the frontal hairline[5]. Inclusion criteria were as follows: FAGA patients of various grades and duration, and their ages ranged from 18 to 50 years. Exclusion criteria were as follows: any cases with chronic hair loss other than AGA as chronic telogen effluvium, diffuse alopecia areata, anagen effluvium, trichotillomania; systemic diseases like hypothyroidism; collagen diseases, such as systemic lupus erythematosus, frontal fibrosing alopecia, and early cicatricial alopecia. Other conditions that need to be ruled out include nutritional deficiencies, such as iron deficiency and any chronic illnesses.

Each patient was subjected to the following: (a) complete history taking, stressing on the age of each participant, duration of the disease, family history, menstrual history, and history of contraceptive methods. (b) Full clinical examination. (c) Punch biopsy from the scalp was taken from each case. (d) Punch biopsies were fixed in 10% neutral buffered formalin, dehydrated in ascending grades of ethanol followed by immersion in xylene then impregnated in paraffin. (e) Several 5 μm thick sections from each block were taken. (f) One slide was stained by hematoxylin and eosin for routine histopathological examination and other sections were mounted on super frost plus slides and stored at room temperature to be stained immunohistochemically. The pathologist found increased numbers of miniaturized, vellus-like hair follicles, the ratio of terminal to vellus-like hairs was less than 3: 1. There was a reduction in follicle size, depth, and hair shaft diameter, with an increased telogen/anagen ratio. Low levels of inflammation were found as lymphocytic microfolliculitis targeting the hair bulge. In our study, we observed the expression of IGF-1R in basal epidermal keratinocytes, follicular outer root sheath, sebacous glands, and hair matrix.

Statistical analysis

Data were fed to the computer and analyzed using IBM SPSS software Package, version 20.0 (IBM Corp., Armonk, New York, USA). Qualitative data were described using number and percent. The Kolmogorov–Smirnov test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, SD, and median. The significance of the obtained results was judged at the 5% level. The used tests were 2; for categorical variables, to compare between different groups, Mann–Whitney test; for abnormally quantitative variables, to compare between two studied groups.


  Results Top


This case–control study included 20 females with different grades of AGA as group I (GI) ranging in age from 27 to 50 years with mean ± SD of 38.55 ± 6.69 and 38.5 as a median value. The control group that represented group II (GII) included 10 age-matched normal females and there was no significant difference between the studied cases and the control with respect to age (P = 0.120). The duration of the disease in the studied cases (GI) ranged from 3 to 12 years with mean ± SD of 5.90 ± 2.51 and 5.0 as a median value, and most cases had a positive family history (75%) [Table 1].
Table 1: Comparison between the two studied groups according to the demographic data

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With respect to the menstrual history, from GI (studied cases) 25% of cases were with no menstruation, 5% had irregular menstruation, and 70% had regular menstruation; and all the cases of GII were with regular menstruation. P value was 0.189, so no significant difference between the two groups with respect to menstruation. Moreover, regarding the history of contraceptive method in GI, 25% of cases did not use contraceptive while 75% of them used it. They used intrauterine device, contraceptive pills, medroxyprogesterone acetate by 50, 15,10% by sequence [Table 2].
Table 2: Comparison between the two studied groups according to menstrual history and the history of contraceptive method

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There was a high significant difference between the two groups according to the degree of intensity and percentage of IGF-1R. From pathological point of view, the degree of intensity was determined by the depth of the marker color. Accordingly, the cases were classified into four degrees, negative meant no color produced by the marker, mild positive degree of intensity meant mild change of the color, moderate positive degree of intensity meant moderate change of the color, highly positive degree of intensity meant strong deep brown color of the marker. GI showed 40% with negative intensity, 40% with mild positivity, and 20%with moderate positivity; while GII showed 100% with high positive intensity, and for the percentage of IGF-1R, it ranged in GI from 0.05 to 0.25 with mean ± SD 0.10 ± 0.08 and median was 0.08. In GII, it ranged from 0.91 to 0.98 with mean ± SD 0.95 ± 0.02 and median was 0.95. P value was 0.001, so there was high significant difference between the two groups according to the degree of intensity and percentage of IGF-1R [Table 3].
Table 3: Comparison between the two studied groups according to the degree of intensity of insulin-like growth factor-1 receptor

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  Discussion Top


AGA is being recognized as a condition with significant effects, including severe psychological stress, depression, negative self-image, and outside perceptions[14],[15]. FPHL is characterized by a reduction in hair density over the crown and frontal scalp with retention of the frontal hairline. IGF-1 is a physiological regulator of hair growth cycle. IGF-1 helps maintain the anagen stage. Primary action of IGF-1 is mediated by binding to its specific receptor, the IGF-1R, present on many cell types in many tissues. Binding to the IGF-1R, a tyrosine kinase receptor, initiates intracellular signaling; IGF-1 is one of the most potent natural activators of the protein kinase B signaling pathway, a stimulator of cell growth and proliferation, and a potent inhibitor of programed cell death[3].

In addition, some hair loss treatments may exert their therapeutic effects via IGF-1. It in itself might also be considered as a new therapeutic option for the treatment for hair loss, particularly AGA as well as alopecia areata. Three percent liposomal IGF-1 in a liquid gel formulation is found to increase both hair growth and thickness in a hamster model. The safety profile is also studied. No evidence of hepatotoxic and myelotoxic side effects has been found[16]. Regarding age, no significant difference between the studied cases and the control, which coincide with the age of patients that[17] collected in their study. According to the family history, from 20 cases, 15 cases had a positive family history, which presented 75%. And so, not all female patients had a positive family history so, the term FPHL in women is the preferred appellation, because not all women with this condition present a clear genetic and androgenetic trait[16]. According to the menstrual history, from GI, 25% of cases were with no menstruation, 5% had irregular menstruation, and 70% had regular menstruation but in GII all cases were with regular menstruation and according to the results, there was no significant difference between the two groups with respect to menstruation. The patients were exposed to clinical examination depending on the pattern of hair loss (shedding vs. thinning) and general examination was carried out. Punch biopsy was taken from each participant and by immunohistochemical staining, the degree of intensity and percentage of IGF-1R were determined for each group (GI and GII). The current study showed no significant relation between IGF-1 expression and all clinical parameters (age, duration of the disease, family history, menstrual history, and history of contraceptive methods). We found that there was a significant difference between the diseased and the normal group with respect to the degree of intensity and the percentage of IGF-1R.


  Conclusion Top


On the basis of the results, it could be concluded that IGF-1R had a role in treating FAGA.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Banka N, Bunagan MJ, Shapiro J. Pattern hair loss in men: diagnosis and medical treatment. Dermatol Clin 2013; 31:129-140.  Back to cited text no. 1
    
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Piraccini BM, Alessandrini A. Androgenetic alopecia. G Ital Dermatol Venereol 2014; 149:15-24.  Back to cited text no. 2
    
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Varothai S, Bergfeld WF. Androgenetic alopecia: an evidence based treatment update. Am J Clin Dermatol 2014; 15:217-230.  Back to cited text no. 4
    
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Sanke S, Chander R, Jain A, Garg T, Yadav P. Acomparison of the hormonal profile of early androgenetic alopecia in men with the phenotypic equivalent of polycystic ovarian syndrome in women. JAMA Dermatol 2016; 152:986-991.  Back to cited text no. 6
    
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Cranwell W, Sinclair R. Male androgenetic alopecia. South Dartmouth, MA: Endo-text. MDText.com Inc.; 2016.  Back to cited text no. 7
    
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Kelly Y, Blanco A, Tosti A. Androgenetic alopecia: an update of treatment options. Drugs 2016; 76:1349-1364.  Back to cited text no. 8
    
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Vano-Galvan S, Camacho F. New treatments for hair loss. Actas Dermo Sifiliogr 2017; 108:221-228.  Back to cited text no. 9
    
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Fong P, Tong HH, Ng KH, Lao CK, Chong CI, Chao CM. In silico prediction of prostaglandin D2 synthase inhibitors from herbal constituents for the treatment of hair loss. J Ethnopharmacol 2015; 175:470-480.  Back to cited text no. 10
    
11.
Premanand RR Androgen modulation of Wnt/B-catenin signaling in androgenetic alopecia. Arch Dermatol Res 2018; 310:391-399.  Back to cited text no. 11
    
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Dinh QQ, Sinclair R. Female pattern hair loss: current treatment concepts. Clin Interv Aging 2007; 2:189-199.  Back to cited text no. 12
    
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Valentinis B, Baserga R. IGF-I receptor signaling in transformation and differentiation. Mol Pathol2001; 54:133-137.  Back to cited text no. 13
    
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Stough D, Stenn K, Haber R, Parsley WM, Vogel JE, Whiting DA, et al. Psychological effects, pathophysiology, and management of androgenetic alopecia in men. Mayo Clinic 2005; 80:1316-1322.  Back to cited text no. 14
    
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Torres F. Androvenetic, diffuse and senescent alopecia in men: practical evaluation and management. Curr Probe Dermatol 2015; 47:33-44.  Back to cited text no. 15
    
16.
Castro RF, Azzalis LA, Feder D, Perazzo FF, Pereira EC, Junqueira VB, et al. Safety and efficacy analysis of liposomal insulin-like growth factor-1 in a fluid gel formulation for hair-loss treatment in a hamster model. Clinical and Experimental Dermatology: Experimental dermatology 2012; 37:909-12.  Back to cited text no. 16
    
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Panchaprateep R, Asawanonda P. Insulin-like growth factor-1: Roles in androgenetic alopecia. Experimental dermatology 2014; 23:216-218.  Back to cited text no. 17
    



 
 
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