Penile development is initiated in the tammar wallaby pouch young during the period when 5α-androstane-3α,17β-diol is secreted by the testes
Abstract
Virilization of the urogenital tract is under the control of testicular androgens in all mammals. In tammar young, prostate differentiation begins between d 20 and d 40 under the control of the testicular androgen 5alpha-androstane-3alpha,17beta-diol (5alpha-adiol), but uncertainties exist about the control of penile development. We performed longitudinal studies up to d 150 of pouch life to define normal penile development and the effects of androgen administration and castration. In control animals the male phallus was longer than the female phallus by d 48. Closure of the urethra in males begins around d 60 and continues to at least d 150. Administration of supraphysiological doses of testosterone to females caused penile development equivalent to that of the male and also induced partial closure of the urethral groove by d 150. Castration of male pouch young at d 25 prevented penile development, whereas the penis in males castrated at d 40, 80, or 120 had partial closure of the urethral groove. Administration of 5alpha-adiol to females from d 20-40 also caused partial closure of the urethral groove and some growth of the phallus at d 150, whereas 5alpha-adiol treatment from d 40-80 or 80-120 caused some penile growth but had little effect on urethral development. These findings, together with the fact that we found no sex differences in plasma levels of testosterone, dihydrotestosterone, 5alpha-adiol, dehydroepiandrosterone, or androstenedione from d 51-227, clearly indicate that the action of 5alpha-adiol between d 20 and 40 imprints later differentiation of the male penis.
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Normal masculinization of the fetus is dependent upon androgen secretion by the testis, and androgens act initially during a critical masculinization programming window.
“Normal masculinization of the fetus is dependent upon androgen secretion by the testis, and androgens act initially during a critical masculinization programming window to ensure normal male reproductive development [3–5].”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [4]
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Cites
Sex Determination and Differentiation
MacLaughlin, D. T., & Donahoe, P. K. (2004) · New England Journal of Medicine · doi:10.1056/nejmra022784 · Cited by 452 · see citing works
Hypospadias in sons of women exposed to diethylstilbestrol in utero: a cohort study
Klip, H., Verloop, J., van Gool, J. D., Koster, M. E., Burger, C. W., & van Leeuwen, F. E. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08152-7 · Cited by 327 · see citing works
Imperato‐McGinley, J., Sanchez, R. S., Spencer, J. R., Yee, B., & Vaughan, E. D. (1992) · Endocrinology · doi:10.1210/endo.131.3.1324152 · Cited by 245 · see citing works
Primary genetic control of somatic sexual differentiation in a mammal
Wai‐Sum, O., Short, R. V., Renfree, M. B., & Shaw, G. (1988) · Nature · doi:10.1038/331716a0 · Cited by 210 · see citing works
Self-citationWilson, J. D., Auchus, R. J., Leihy, M. W., Guryev, O. L., Estabrook, R. W., Osborn, S. M., Shaw, G., & Renfree, M. B. (2003) · Endocrinology · doi:10.1210/en.2002-220721 · Cited by 172 · see citing works
Self-citationSex determination in marsupials: evidence for a marsupial—eutherian dichotomy
Renfree, M. B., & Short, R. V. (1988) · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · doi:10.1098/rstb.1988.0112 · Cited by 156 · see citing works
Self-citationSex steroid imprinting of the immature prostate. Long-term effects.
Rajfer, J., & Ds, C. (1978) · PubMed · Cited by 108 · see citing works
Shaw, G., Renfree, M. B., Short, R. V., & W.-S., O. (1988) · Development · doi:10.1242/dev.104.4.689 · Cited by 106 · see citing works
Self-citationProstate formation in a marsupial is mediated by the testicular androgen 5α-androstane-3α,17β-diol
Shaw, G., Renfree, M. B., Leihy, M. W., Shackleton, C. H. L., Roitman, E., & Wilson, J. D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220412297 · Cited by 101 · see citing works
Self-citationRenfree, M. B., Wai‐Sum, O., Short, R. V., & Shaw, G. (1996) · Anatomy and Embryology · doi:10.1007/bf00195006 · Cited by 99 · see citing works
Self-citationPenis and testicular size in patients with growth hormone insufficency.
Laron, Z., & Sarel, R. (1970) · Acta Endocrinologica · doi:10.1530/acta.0.0630625 · Cited by 96 · see citing works
URETHRAL DEVELOPMENT IN THE FETAL RABBIT AND INDUCTION OF HYPOSPADIAS: A MODEL FOR HUMAN DEVELOPMENT
Kurzrock, E. A., Jegatheesan, P., Cunha, G. R., & Baskin, L. S. (2000) · The Journal of Urology · doi:10.1016/s0022-5347(05)67107-8 · Cited by 79 · see citing works
Burrows, H. (1935) · The American Journal of Cancer · doi:10.1158/ajc.1935.490 · Cited by 72 · see citing works
Steroid Hormone Content of the Gonads of the Tammar Wallaby during Sexual Differentiation1
Renfree, M. B., Wilson, J. D., Short, R. V., Shaw, G., & George, F. W. (1992) · Biology of Reproduction · doi:10.1095/biolreprod47.4.644 · Cited by 66 · see citing works
Self-citationManipulation of Marsupial Embryos and Pouch Young
Renfree, M. B., & Tyndale‐Biscoe, C. H. (1978) · Elsevier eBooks · doi:10.1016/b978-0-12-201850-3.50020-6 · Cited by 63 · see citing works
Self-citationYücel, S., Cavalcanti, A. G., Desouza, A., Wang, Z., & Baskin, L. S. (2003) · British Journal of Urology · doi:10.1111/j.1464-410x.2003.04511.x · Cited by 56 · see citing works
Griffin, J. E. (2001) · Medical Entomology and Zoology · Cited by 55 · see citing works
Anderson, C. A., & Clark, R. L. (1990) · Teratology · doi:10.1002/tera.1420420505 · Cited by 53 · see citing works
The Endocrine Role in Mammalian Sexual Differentiation
Wilson, J. D., GEORGE, F. W., & Renfree, M. B. (1995) · Elsevier eBooks · doi:10.1016/b978-0-12-571150-0.50021-4 · Cited by 51 · see citing works
Self-citationPrimary Genetic-Control of Sexual-Differentiation in Marsupials
Shaw, G., Renfree, M. B., & Short, R. F. (1989) · Australian Journal of Zoology · doi:10.1071/zo9890443 · Cited by 47 · see citing works
Self-citationThe marsupial model for male phenotypic development
Wilson, J. D., Shaw, G., Leihy, M. W., & Renfree, M. B. (2002) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(01)00525-2 · Cited by 42 · see citing works
Self-citationEnigmatic Features of Penile Development and Functions
Williams-Ashman, H. G. (1990) · Perspectives in biology and medicine · doi:10.1353/pbm.1990.0008 · Cited by 40 · see citing works
Growth hormone deficiency presenting under age 2 years.
Herber, S. M., & Milner, R. D. G. (1984) · Archives of Disease in Childhood · doi:10.1136/adc.59.6.557 · Cited by 37 · see citing works
Imprinting by Neonatal Sex Steroids on the Structure and Function of the Mature Mouse Prostate1
Singh, J., & Handelsman, D. J. (1999) · Biology of Reproduction · doi:10.1095/biolreprod61.1.200 · Cited by 36 · see citing works
Brown, Nevison, Fraser, & Dixson (1999) · International Journal of Andrology · doi:10.1046/j.1365-2605.1999.00158.x · Cited by 34 · see citing works
Leihy, M. W., Shaw, G., Renfree, M. B., & Wilson, J. D. (2002) · Endocrinology · doi:10.1210/endo.143.7.8917 · Cited by 33 · see citing works
Self-citationWilson, J. D., George, F. W., Shaw, G., & Renfree, M. B. (1999) · Biology of Reproduction · doi:10.1095/biolreprod61.2.471 · Cited by 32 · see citing works
Self-citationTyndale‐Biscoe, C. H., & Hinds, L. A. (1989) · Reproduction Fertility and Development · doi:10.1071/rd9890243 · Cited by 31 · see citing works
Leihy, M. W., Shaw, G., Wilson, J. D., & Renfree, M. B. (2001) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(01)00527-5 · Cited by 30 · see citing works
Self-citationThe influence of the anti-androgen flutamide on early sexual differentiation of the marsupial male
Lucas, J. C., Renfree, M. B., Shaw, G., & Butler, C. M. (1997) · Reproduction · doi:10.1530/jrf.0.1090205 · Cited by 28 · see citing works
Self-citationThe influence of estrogen on the developing male marsupial
Renfree, M. B., Coveney, D., & Shaw, G. (2001) · Reproduction Fertility and Development · doi:10.1071/rd00123 · Cited by 27 · see citing works
Self-citationDevelopment of the penis and clitoris in the tammar wallaby, Macropus eugenii
Butler, C. M., Shaw, G., & Renfree, M. B. (1999) · Anatomy and Embryology · doi:10.1007/s004290050243 · Cited by 26 · see citing works
Self-citationRYHORCHUK, A. R., Shaw, G., Butler, C. M., & Renfree, M. B. (1997) · Journal of Andrology · doi:10.1002/j.1939-4640.1997.tb01892.x · Cited by 26 · see citing works
Self-citationRYHORCHUK, A. R., Shaw, G., Butler, C. M., et al. (1997) · PubMed · Cited by 25 · see citing works
Self-citationCoveney, D., Shaw, G., Hutson, J., & Renfree, M. B. (2002) · Reproduction · doi:10.1530/rep.0.1240865 · Cited by 16 · see citing works
Self-citationCoveney, D., Shaw, G., & Renfree, M. B. (2002) · Reproduction · doi:10.1530/rep.0.1240073 · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Renfree MB 1994 Sexual dimorphisms of the gonads and the reproductive tracts of marsupial mammals. In: Short RV, Balaban E, eds. The differences between the sexes. Cambridge, UK: Cambridge University Press; 213-230
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O’Shaughnessy, P. J., Antignac, J. P., Le Bizec, B., Morvan, M.-L., Svechnikov, K., Söder, O., Savchuk, I., Monteiro, A., Soffientini, U., Johnston, Z. C., et al. (2019) · PLOS Biology · doi:10.1371/journal.pbio.3000002 · Cited by 177 · see citing works
Fung, K.-M., Samara, E. N. S., Wong, C., Metwalli, A., Krlin, R., Bane, B., Liu, C. Z., Yang, J. T., Pitha, J. V., Culkin, D. J., et al. (2006) · Endocrine Related Cancer · doi:10.1677/erc.1.01048 · Cited by 129 · see citing works
Evolutionary History and Functional Characterization of Androgen Receptor Genes in Jawed Vertebrates
Ogino, Y., Katoh, H., Kuraku, S., & Yamada, G. (2009) · Endocrinology · doi:10.1210/en.2009-0523 · Cited by 94 · see citing works
Glickman, S. E., Short, R. V., & Renfree, M. B. (2005) · Hormones and Behavior · doi:10.1016/j.yhbeh.2005.07.013 · Cited by 82 · see citing works
Self-citationShaw, G., & Renfree, M. B. (2014) · Sexual Development · doi:10.1159/000363432 · Cited by 61 · see citing works
Self-citationShaw, G., Fenelon, J., Sichlau, M., Auchus, R. J., Wilson, J. D., & Renfree, M. B. (2006) · Endocrinology · doi:10.1210/en.2005-1251 · Cited by 32 · see citing works
Self-citationDifferential expression of WNT4 in testicular and ovarian development in a marsupial
Yu, H., Pask, A. J., Shaw, G., & Renfree, M. B. (2006) · BMC Developmental Biology · doi:10.1186/1471-213x-6-44 · Cited by 32 · see citing works
Self-citationOgino, Y., Miyagawa, S., Katoh, H., Prins, G. S., Iguchi, T., & Yamada, G. (2011) · Evolution & Development · doi:10.1111/j.1525-142x.2011.00482.x · Cited by 32 · see citing works
Wolffian duct differentiation by physiological concentrations of androgen delivered systemically
Renfree, M. B., Fenelon, J. C., Wijiyanti, G., Wilson, J. D., & Shaw, G. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.07.040 · Cited by 31 · see citing works
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Hickford, D. E., Frankenberg, S., & Renfree, M. B. (2009) · Cold Spring Harbor Protocols · doi:10.1101/pdb.emo137 · Cited by 28 · see citing works
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- Authors
- Leihy, M. W., Shaw, G., Wilson, J. D., & Renfree, M. B.
- Affiliations
- The University of Melbourne (AU)
- Department of Zoology (M.W.L., G.S., J.D.W., M.B.R.), University of Melbourne, Victoria 3010, Australia
- Corresponding author
- Renfree, Marilyn B.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2004-07-01
- Volume
- 145
- Issue
- 7
- Pages
- 3346-3352
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2089315944
- Cited by
- 38
- References
- 36
- Citations by year
- 2024: 2 · 2023: 4 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 4
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council (208911)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Urology › Urological Disorders and Treatments
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- penile development, tammar wallaby, pouch young, 5α-androstane-3α,17β-diol, testicular androgens, testosterone, castration, sexual differentiation, dihydrotestosterone, androstenedione, dehydroepiandrosterone, androgen administration
- MeSH terms
- Androgens, Animals, Female, Macropodidae, Longitudinal Studies, Male, Orchiectomy, Oxidation-Reduction, Penis, Sex Differentiation, Testis, Testosterone, Tritium, Urethra, Androstane-3,17-diol
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