J Invest Dermatol. 1993;101:50S

Organization and expression of hair follicle genes.

Rogers GE, Powell BC.

Edited for blog

Several families of proteins are expressed in the growth of hair and an estimated 50-100 proteins constitute the final hair fiber. The cumbersome nomenclature for naming these different proteins has led to a proposal to modify that which is currently used for epidermal keratins. Investigations of the organization of hair genes indicate that the members of each family are clustered in the genome and their expression could be under some general control. Interestingly, the protein called trichohyalin, markedly distinct from the hair proteins, is produced in the inner root sheath cells and the gene for it has been found to be located at the same human chromosome locus as the genes for profilaggrin, involucrin, and loricrin. ...snip..In the sheep, the patterns of expression in hair differentiation are particularly interesting insofar as there are distinct segments of para- and orthocortical type cells that have significantly different pathways of expression. The testing of candidate hair-specific regulatory sequences by mouse transgenesis has produced several interesting hair phenotypes. Transgenic sheep over-expressing keratin genes but showing no hair regrowth change have been obtained and compared with the equivalent transgenic hair-loss mice. Studies of the effects of amino acid supply on the rate of hair regrowth have demonstrated that with cysteine supplementation of sheep a perturbation occurs in which there is a markedly increased level of only one type of mRNA and the ration of para- to orthocortical cells is increased....

Dermatol Clin. 1990;8(2):367

The therapeutic use of topical minoxidil.DeVillez RL.

edited for blog use

Topical minoxidil is a hair regrowth stimulating agent that stimulates the hair follicle via the vasoactive metabolite minoxidil sulfate without any evidence of antiandrogen activity or an effect on the immune system. snip.. The most common adverse reactions are limited to irritant and allergic contact dermatitis on the scalp. The use of retinoic acid with topical minoxidil has been disappointing relative to the increase in systemic exposure. The value of topical minoxidil as an adjunct for the hair transplant procedure and its effect on hair loss from chemotherapy are being evaluated.

hair loss treatment

Transplantation. 1987;44(1):83

Long-term survival of skin allografts in rats treated with topical cyclosporine.

Lai CS,et al

Treatment with topical cyclosporine (CsA) was studied in skin allografts from Buffalo to Lewis rats. ....snip.. Most grafts were rejected when CsA blood levels fell below 200 ng/ml. Direct administration of topical CsA onto the allografts resulted in longer survival compared with those applied on the normal recipient skin 6 cm distal to the allografts, with both high and low doses. Locally high concentrations of CsA in allografts may play an important role in prolongation of graft survival. Minimal cell infiltration and loss of hair follicles were the main histological features in long-surviving allografts (greater than 120 days).

J Cutan Pathol.Oct;13(5):363

Markers of immunologic injury in progressive alopecia areata

.Peereboom-Wynia JD, et al

In a selected group of 8 patients with progressive hair loss due to alopecia areata (AA) leading to AA universalis, immunological aspects (in the peripheral blood and the tissue) were studied during the period of the initial attack of the disease. The peripheral T-cell helper/suppressor ratio appeared not to be a reliable parameter for the disease activity. The intrabulbar and peribulbar distribution of T-cells, Langerhans cells and of HLA-DR expression in and around the anagen hair follicles in the progressive areas of the disease (region of exclamation-mark hairs) may suggest a T-cell-mediated injury primarily in the peribulbar regions of the follicles. The data presented tend to support the possibility that in the early development of AA, the dermal pailla (capillary network?) may be the prime target of immunologic injury. Hair regrowth

Gynecol Endocrinol1992;6(2):85-90.

Is 3 alpha, 17 beta-androstanediol-glucuronide a diagnostic marker in women with androgenic manifestations?

Vogt C, et al

3 alpha, 17 beta-androstanediol-glucuronide (Adiol-G) has been described as a marker of local androgen excess due to the increased activity of 5 alpha-reductase in the cells of the hair follicles. In order to test the diagnostic value of Adiol-G, the serum level was compared to that of testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione and to the body mass index in 44 women with androgenic symptoms such as pattern hair loss (Group I), 27 women with menstrual disturbances but no androgenic symptoms (Group II), and 48 healthy women (Group III) who served as controls. ....snip.. When Adiol-G and testosterone were simply classified as 'normal' or 'increased' (Adiol-G 9.4 nmol/l; testosterone greater than 2.4 nmol/l), higher than normal values of the former were found in the presence of normal testosterone in only 4% of the cases. It is concluded that the level of Adiol-G generally parallels that of testosterone. Consequently, it does not seem to be an effective marker of peripheral androgen excess.

Hair loss and hair loss regrowth

Arch Dermatol Res. 1977;258:33-40.

Ultrastructure of the contrasting types of keratinization seen in the tail epidermis of the laboratory mouse

Spearman RI, Hardy JA.

The mouse tail epidermis undergoes contrasting forms of keratinization. Around the hair follicle there is a granular layer containing keratohyalin granules, and nuclei are absent from the horny layer. In the scale regions keratohyalin is not formed and nuclear remnants are retained in the horny cells as in parakeratosis generally. These findings from light microscopy were confirmed by transmission electron microscopy. ...snip... The change from living epidermal cells to dead keratinized cells was abrupt in both the follicular and scale regions. In both sites the plasma membranes of the horny cells were thickened and there was a cytoplasmic meshwork of microfibrils in the cells.

hair loss and hair regrowth

Dermatol Surg. 1997 Sep;23(9):785-99.

The aesthetics of follicular transplantation.

Bernstein RM,

BACKGROUND: Follicular transplantation is a method of hair restoration surgery that uses hair in its naturally occurring groups, called follicular units. Using the follicular unit exclusively in the transplant, the surgeon can create hair patterns that closely mimic nature. OBJECTIVE: To focus on various aesthetic aspects of the follicular transplantation procedure including hair distribution, hairline design, and crown restoration. Racial variations that affect the transplant will also be examined. METHODS: Follicular transplantation is performed according to techniques detailed in a previous publication (Bernstein et al. Int J Aesthet Rest Surg 1995; 3: 119-32). RESULTS: Excellent cosmetic results can be achieved when aesthetic decisions are made that allow the surgeon to recreate hair patterns already provided by nature. A case study will be presented. CONCLUSIONS: The small size of follicular implants enables the surgeon great versatility in their placement. Follicular transplantation will ensure a natural looking transplant if used with good aesthetic judgment and careful planning.

J Am Acad Dermatol. 1980 Dec;3(6):623-6.

Analysis of hair from alopecia congenita.Baden HP, Kubilus J.

Two patients with alopecia congenita had short vellus hairs of the scalp but some apparently normal-sized hairs in other areas. Both fibrous and matrix proteins were detected in the scalp hairs by polyacrylamide gel electrophoresis (PAGE), and x-ray diffraction analysis revealed a normal alpha pattern. Amino acid analysis showed a decreased cystine content suggesting a quantitative or qualitative change in the matrix component. Scanning electron microscopic examination revealed pits and bulges in the cuticle cells which may be related to wearing a wig. The data suggest a defect in the development of the follicle rather than an abnormality in a component of the hair.

PMID: 7204679

hair loss blog

Hautarzt. 1994 Jun;45(6):360-3

Hair growth promoters in androgenetic alopecia. Expectations and reality

Schell H, Kiesewetter F, Hornstein OP.

Androgenetic hair loss is the most frequent reason for the topical application of hair-growth-promoting agents. Such preparations should arrest or even reverse androgen-induced hair follicle regression as well as prolonging the hair cycles, especially of the shortened anagen phase, and thus protect from increased hair loss. True evidence of drug effects on hair regrowth is problematic, since trichograms, the method chiefly applied by the manufacturers, fail to reveal every factor involved in the follicular activity, especially the duration of anagen stage. For example, an increase in the anagen rate does not always reflect a lengthening of the anagen stage, but may also be due to shortened hair cycles. Accordingly, drug effects on hair growth should be investigated by methods that analyse the cell cycle kinetics. For this approach DNA-flowcytometry of the outer root sheath in plucked anagen hairs and of complete anagen hair bulbs taken by micropreparative techniques from scalp biopsies offers a reproducible method for quick and reliable evaluation of hair growth.

Hautarzt. 1991 Mar;42(3):168-72.

Hyperprolactinemia and hypophyseal hypothyroidism as cofactors in hirsutism and androgen-induced alopecia in women

Schmidt JB, Lindmaier A, Spona J.
II. Universitäts-Hautklinik, Wien.

A more comprehensive hormonal diagnosis than has previously been performed shows that androgen-dependent diseases of hair regrowth are due to more varied hormonal disturbances than elevated androgen serum levels alone. In 46 female patients with androgenic hair loss and 27 patients with hirsutism, the levels of the androgens testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulphate and 17-hydroxyprogesterone and of sex hormone-binding globulin, cortisol, oestradiol and the hypophyseal hormones follicle-stimulating hormone and luteinizing hormone were determined and compared with the hormone levels of 27 female patients without endocrine disorders. Of the androgens, only androstenedione showed a slightly significant elevation in hirsutism. Cortisol was elevated significantly in androgenic hair loss, and with a low degree of significance in hirsutism. In view of the complex hormonal interactions of thyroxin, prolactin and androgens and thyroid hormones the thyrotropin-releasing hormone (TRH)-stimulation test was performed in 38 female patients with androgenic hair loss and 27 with hirsutism, and the results were compared with those recorded in 45 female control persons. The test is based on feedback mechanisms between hypothalamic TRH and hypophyseal TSH and prolactin and peripheral thyroid hormones. Baseline concentrations of TSH prior to stimulation were significantly elevated in hirsutism, while in androgenic hair loss both baseline and stimulated TSH levels were significantly elevated; thus, hypothyroidism is a significant finding in both clinical pictures. snip

alopecia universalis in a woman with IDDM
Endocrinol Jpn. 1991 Aug;38(4):445-9.

Simultaneous occurrence of SIADH, secondary hypogonadism and alopecia universalis in a woman with IDDM.
Yasutomo Y, et al

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH), hypothalamic hypogonadism and alopecia universalis occurred in a 31-year-old female with insulin-dependent diabetes mellitus (IDDM). Despite various clinical investigations and careful observation for 20 months, the cause and pathogenesis of SIADH and hypothalamic hypogonadism were not elucidated. The complex of these disorders had not been described. The presence of IDDM and hair loss associated with alopecia universalis, in which an autoimmune process has been assumed to be involved, is interesting in considering the pathogenesis of the SIADH and hypothalamic hypogonadism.

PMID: 1666359

Hair follicle proteins
Eur J Cell Biol. 1990 Aug;52(2):359-72.

Keratins 1 and 10 or homologues as regular constituents of inner root sheath and cuticle cells in the human hair follicle.

Stark HJ, et al.

Morphological maturation of the inner root sheath (IRS) and cuticle of the human hair follicle reveals analogies to differentiation processes in other keratinizing epithelia. Detailed biochemical analysis of respective differentiation products, however, has been largely restricted by their low solubility. Herein we provide further evidence for the existence of K1 and K10-derivatives in IRS and hair cuticle based on protein analysis of isolated fractions and immunofluorescence in situ, substantiating our earlier data (Stark, H. J., et al. Differentiation 35, 236-248 (1987)). Extracts from both compartments showed on two-dimensional (2D)-polyacrylamide gels a group of presumptive K1 and K10-turnover products in a wide pI (basic to acidic) and Mr range (56,000-65,000), named IC-I to III and IC-IV, respectively. These components (also found in nail plate) reacted with specific antibodies (to K1 and K10) on Western blots. Weak but distinctive radiolabeling of presumptive precursor spots close to authentic K1 and K10, respectively, and their presence in lower follicle fractions (distant from infundibulum) largely precluded epidermal contamination. Two-dimensional tryptic peptide maps of excised 2D spots from the IC-I to III series revealed high homology to K1, and those from IC-IV components to K10. Immunodetection in frozen sections was improved by trypsin pretreatment and showed distinguished staining for K1 and K10 in IRS ranging from the lower bulbus region up to the “keratinizing zone” of the follicle. Above, the reaction was abruptly abolished which coincides with ultrastructural “melting” of distinct filaments in the intracellular matrix. Thus, our data suggest that differentiation in these follicular compartments (IRS and cuticle) might follow common principles of keratinization.

Hair loss treatment and hair regrowth

J Clin Endocrinol Metab. 1990 Aug;71(2):335-9

Ketoconazole therapy for women with acne and/or hirsutism.
Venturoli S, et al

The effects of ketoconazole, a synthetic imidazole derivate, were evaluated in 42 women affected by acne (17 cases) and/or hirsutism (36 cases) treated with 400 mg/day for 3-6 months. Androstenedione, total and free testosterone, 5 alpha dihydrotestosterone and dehydroepiandrosterone levels progressively dropped during treatment while 17 alpha hydroxyprogesterone, estradiol, ACTH, cortisol, LH and FSH levels increased. Dehydroepiandrosterone sulfate decreased only towards the end of treatment, while estrone, sex hormone binding globulin, and PRL remained unchanged. Daily mean +/- SD rate of hair growth, measured by a special image analysis processor, decreased within 3 months of therapy from 0.258 +/- 0.058 to 0.184 +/- 0.039 mm/day (P less than 0.02) and mean +/- SD hair diameter from 0.123 +/- 0.015 to 0.110 +/- 0.013 mm (P less than 0.05) together with decreasing hormone levels. The therapeutic effects of ketoconazole on hirsutism was evident at 6 months in only 14 subjects, while no significant change in hirsutism score was recorded in 22 women who failed to complete the therapy. Acne improved in all cases. Several side effects and complications arose during treatment, such as headache, nausea, scalp hair loss, hepatitis, and biochemical changes. Even though ketoconazole improves hyperandrogenism, only selected patients are eligible for treatment as scrupulous monitoring is required.

Drug Ther Bull. 1989 Sep 18;27(19):74-6.

Topical minoxidil does little for male pattern hair loss.

PMID: 2519132

hair loss blog

Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss

J Am Acad Dermatol. 2001 Sep;45(3 Suppl):S81-6.

Whiting DA.

In androgenetic alopecia, or pattern hair loss, follicles undergo miniaturization, shrinking from terminal to vellus-like hairs. Traditionally, this process is thought to progress gradually over a number of follicular cycles. However, it is unlikely that miniaturization can be explained only by a series of progressively shorter anagen cycles. Simple calculations show that this process would take too long for significant miniaturization to occur secondary to shorter anagen cycles alone, especially in view of the latent lag period seen in pattern hair loss that occurs between the loss of a telogen hair and the appearance of an anagen hair. Evidence is presented to support a new concept that miniaturization is an abrupt, large-step process that also can be reversed in 1 hair cycle, as has been shown clinically, with confirmatory histologic evidence, in patients with pattern hair loss responding to finasteride treatment. It is hypothesized that the miniaturization seen with pattern hair loss may be the direct result of reduction in the cell number and, hence, size of the dermal papilla.

Postgrad Med. 1982 Oct;72(4):231-6, 243-6.

Nonscarring hair loss disorders: the basis for recognition and treatment.

Herten RJ.

Hair loss can be assessed objectively by examining a hair pull sample for stage of growth and hair shaft diameter, getting an estimate of average daily hair loss, and mapping scalp hair density. The history of the loss, the clinical picture, and the growth stage and diameter of the hair when lost all help to establish the type of loss. Hair regrowth occurs without treatment in most types of hair loss. There is as yet no effective treatment for pattern or senescent alopecia, although in women the loss can now be retarded somewhat.

childhood acute lymphoblastic leukemia
Blood. 1983 Feb;61(2):297-303.

Efficacy and morbidity of central nervous system “prophylaxis” in childhood acute lymphoblastic leukemia: eight years’ experience with cranial irradiation and intrathecal methotrexate.

Inati A, et al

Between 1972 and 1979, 214 children with acute lymphoblastic leukemia and no evidence of central nervous system (CNS) disease prior to CNS prophylaxis were treated with 2400 rad cranial irradiation and concurrent intrathecal methotrexate. Only nine children developed CNS leukemia; five of them in the CNS only and four concurrently in the CNS and another site. Major acute effects of CNS prophylaxis were seizures in seven patients (3%). Sixty-nine children who had a minimum follow-up of 4 yr were evaluable for late effects of therapy. Small cataracts, incomplete hair regrowth, and learning disabilities were noted. The latter occurred in 18% of patients, an incidence similar to that encountered in a normal community of school-age children. However, the incidence of learning disabilities in patients who were under 5 yr of age at the time of diagnosis was much higher, 35%. We conclude that the combination of cranial irradiation and intrathecal methotrexate was highly efficacious. The incidence and severity of neuropsychologic abnormalities, the principal late morbidity of this treatment program, varies among reporting institutions. Prospective longitudinal studies of neuropsychologic function are necessary to better define the incidence of abnormalities. Future programs should attempt to decrease late morbidity, but must also assure equal efficacy and improve overall disease-free survival.