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. 1976 Aug;58(2):345–350. doi: 10.1172/JCI108478

Male pseudohermaphroditism presumably due to target organ unresponsiveness to androgens. Deficient 5alpha-dihydrotestosterone binding in cultured skin fibroblasts.

M Kaufman, C Straisfeld, L Pinsky
PMCID: PMC333189  PMID: 182718

Abstract

Maximum specific 5alpha-dihydrotestosterone (DHT) binding activity (Bmax) had been measured in intact confluent monolayers representing fibroblast strains derived form nongenital and genital (labium majus) skin of normal individuals and of 11 patients fulfilling the clinicogenetic criteria of complete testicular feminization (TF). Nine labium majus strains from adult females had a mean Bmax value three times greater than that of seven nongenital strains from adult females (33 vs. 11 fmol/mg cell protein). The Bmax results for 13 adult nongenital strains varied from 5.6 to 23.3 fmol/mg protein; the values for males and females had very similar means and ranges. The variation could not be correlated with the chronologic age of adult skin explant donors or with the in vitro age (mean population doubling level) of the cultures assayed. The Bmax activities of three nongenital strains from normal infants (two male, one female) did not exceed 5 fmol/mg protein. Seven of eight nongenital TF strains had Bmax values below 2 fmol/mg protein; the value for the eighth coincided with the lower limit of normal adults. The lower limit of DHT binding in normal labium majus strains was 15 fmol/mg protein. Three of five labial strains from patients with TF had Bmax values close to zero; the other two fell between 10 and 15 fmol/mg protein. It is apparant that labial skin fibroblast strains from clinically homogeneous patients with TF had highly variable degrees of DHT binding deficiency, and that they permit a more reliable diagnosis of severe and intermediate degrees of DHT binding deficiency than do strains of nongenital skin fibroblasts.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amrhein J. A., Meyer W. J., 3rd, Jones H. W., Jr, Migeon C. J. Androgen insensitivity in man: evidence for genetic heterogeneity. Proc Natl Acad Sci U S A. 1976 Mar;73(3):891–894. doi: 10.1073/pnas.73.3.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bricaire H., Luton J. P., Laudat P., Legrand J. C., Turpin G., Corvol P., Lemmer M. A new male pseudo-hermaphroditism associated with hypertension due to a block of 17 -hydroxylation. J Clin Endocrinol Metab. 1972 Jul;35(1):67–72. doi: 10.1210/jcem-35-1-67. [DOI] [PubMed] [Google Scholar]
  3. Espiner E. A., Veale A. M., Sands V. E., Fitzgerald P. H. Familial syndrome of streak gonads and normal male karyotype in five phenotypic females. N Engl J Med. 1970 Jul 2;283(1):6–11. doi: 10.1056/NEJM197007022830102. [DOI] [PubMed] [Google Scholar]
  4. Givens J. R., Wiser W. L., Summitt R. L., Kerber I. J., Andersen R. N., Pittaway D. E., Fish S. A. Familial male pseudohermaphroditism without gynecomastia due to deficient testicular 17-ketosteroid reductase activity. N Engl J Med. 1974 Oct 31;291(18):938–944. doi: 10.1056/NEJM197410312911805. [DOI] [PubMed] [Google Scholar]
  5. HAYFLICK L. THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS. Exp Cell Res. 1965 Mar;37:614–636. doi: 10.1016/0014-4827(65)90211-9. [DOI] [PubMed] [Google Scholar]
  6. Hook E. B. Behavioral implications of the human XYY genotype. Science. 1973 Jan 12;179(4069):139–150. doi: 10.1126/science.179.4069.139. [DOI] [PubMed] [Google Scholar]
  7. Imperato-McGinley J., Guerrero L., Gautier T., Peterson R. E. Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science. 1974 Dec 27;186(4170):1213–1215. doi: 10.1126/science.186.4170.1213. [DOI] [PubMed] [Google Scholar]
  8. Kahlenberg A. Lack of stereospecificity of glucose binding to human erythrocyte membrane protein upon reduction with sodium borohydride. Biochem Biophys Res Commun. 1969 Aug 15;36(4):690–695. doi: 10.1016/0006-291x(69)90361-1. [DOI] [PubMed] [Google Scholar]
  9. Kaufman M., Pinsky L. Letter: Skin biopsy site and biology of fibroblast strains. Lancet. 1973 Nov 24;2(7839):1202–1203. doi: 10.1016/s0140-6736(73)92962-0. [DOI] [PubMed] [Google Scholar]
  10. Kaufman M., Pinsky L., Straisfeld C., Shanfield B., Zilahi B. Qualitative differences in testosterone metabolism as an indication of cellular heterogeneity in fibroblast monolayers derived from human preputial skin. Exp Cell Res. 1975 Nov;96(1):31–36. doi: 10.1016/s0014-4827(75)80033-4. [DOI] [PubMed] [Google Scholar]
  11. Keenan B. S., Meyer W. J., 3rd, Hadjian A. J., Jones H. W., Migeon C. J. Syndrome of androgen insensitivity in man: absence of 5 alpha-dihydrotestosterone binding protein in skin fibroblasts. J Clin Endocrinol Metab. 1974 Jun;38(6):1143–1146. doi: 10.1210/jcem-38-6-1143. [DOI] [PubMed] [Google Scholar]
  12. Keenan B. S., Meyer W. J., Hadjian A. J., Migeon C. J. Androgen receptor in human skin fibroblasts. Characterization of a specific 17beta-hydroxy-5alpha-androstan-3-one-protein complex in cell sonicates and nuclei. Steroids. 1975 Apr;25(4):535–552. doi: 10.1016/0039-128x(75)90030-6. [DOI] [PubMed] [Google Scholar]
  13. Kirkland R. T., Kirkland J. L., Johnson C. M., Horning M. G., Librik L., Clayton G. W. Congenital lipoid adrenal hyperplasia in an eight-year-old phenotypic female. J Clin Endocrinol Metab. 1973 Mar;36(3):488–496. doi: 10.1210/jcem-36-3-488. [DOI] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. MORRIS J. M., MAHESH V. B. FURTHER OBSERVATIONS ON THE SYNDROME, "TESTICULAR FEMINIZATION". Am J Obstet Gynecol. 1963 Nov 15;87:731–748. [PubMed] [Google Scholar]
  16. Meyer W. J., 3rd, Migeon B. R., Migeon C. J. Locus on human X chromosome for dihydrotestosterone receptor and androgen insensitivity. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1469–1472. doi: 10.1073/pnas.72.4.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Moore R. J., Griffin J. E., Wilson J. D. Diminished 5alpha-reductase activity in extracts of fibroblasts cultured from patients with familial incomplete male pseudohermaphroditism, type 2. J Biol Chem. 1975 Sep 25;250(18):7168–7172. [PubMed] [Google Scholar]
  18. Mulay S., Finkelberg R., Pinsky L., Solomon S. Metabolism of 4- 14 C-testosterone by serially subcultured human skin fibroblasts. J Clin Endocrinol Metab. 1972 Jan;34(1):133–143. doi: 10.1210/jcem-34-1-133. [DOI] [PubMed] [Google Scholar]
  19. Pinsky L., Finkelberg R., Straisfeld C., Zilahi B., Kaufman M., Hall G. Testosterone metabolism by serially subcultured fibroblasts from genital and nongenital skin of individual human donors. Biochem Biophys Res Commun. 1972 Jan 31;46(2):364–369. doi: 10.1016/s0006-291x(72)80147-5. [DOI] [PubMed] [Google Scholar]
  20. Pinsky L., Miller J., Shanfield B., Watters G., Wolfe L. S. GM1 gangliosidosis in skin fibroblast culture: enzymatic differences between types 1 and 2 and observations on a third variant. Am J Hum Genet. 1974 Sep;26(5):563–577. [PMC free article] [PubMed] [Google Scholar]
  21. Schneider E. L., Stanbridge E. J., Epstein C. J. Incorporation of 3H-uridine and 3H-uracil into RNA: a simple technique for the detection of mycoplasma contamination of cultured cells. Exp Cell Res. 1974 Mar 15;84(1):311–318. doi: 10.1016/0014-4827(74)90411-x. [DOI] [PubMed] [Google Scholar]
  22. Schneider G., Genel M., Bongiovanni A. M., Goldman A. S., Rosenfield R. L. Persistent testicular delta5-isomerase-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) deficiency in the delta5-3beta-HSD form of congenital adrenal hyperplasia. J Clin Invest. 1975 Apr;55(4):681–690. doi: 10.1172/JCI107977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sibley C. H., Tomkins G. M. Mechanisms of steroid resistance. Cell. 1974 Aug;2(4):221–227. doi: 10.1016/0092-8674(74)90014-2. [DOI] [PubMed] [Google Scholar]
  24. Strickland A. L., French F. S. Absence of response to dihydrotestosterone in the syndrome of testicular feminization. J Clin Endocrinol Metab. 1969 Sep;29(9):1284–1286. doi: 10.1210/jcem-29-9-1284. [DOI] [PubMed] [Google Scholar]
  25. Walsh P. C., Madden J. D., Harrod M. J., Goldstein J. L., MacDonald P. C., Wilson J. D. Familial incomplete male pseudohermaphroditism, type 2. Decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. N Engl J Med. 1974 Oct 31;291(18):944–949. doi: 10.1056/NEJM197410312911806. [DOI] [PubMed] [Google Scholar]
  26. Wilson J. D., Harrod M. J., Goldstein J. L., Hemsell D. L., MacDonald P. C. Familial incomplete male pseudohermaphroditism, type 1. Evidence for androgen resistance and variable clinical manifestations in a family with the Reifenstein syndrome. N Engl J Med. 1974 May 16;290(20):1097–1103. doi: 10.1056/NEJM197405162902001. [DOI] [PubMed] [Google Scholar]
  27. Zachmann M., Völlmin J. A., Hamilton W., Prader A. Steroid 17,20-desmolase deficiency: a new cause of male pseudohermaphroditism. Clin Endocrinol (Oxf) 1972 Oct;1(4):369–385. doi: 10.1111/j.1365-2265.1972.tb00407.x. [DOI] [PubMed] [Google Scholar]
  28. von Westarp C., Killinger D. W., Volpé R. A case of testicular feminization with XYY karyotype. Clin Endocrinol (Oxf) 1974 Oct;3(4):447–455. doi: 10.1111/j.1365-2265.1974.tb02816.x. [DOI] [PubMed] [Google Scholar]

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