{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:19:23Z","timestamp":1790515163042,"version":"4.1.0"},"reference-count":455,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiological Reviews"],"published-print":{"date-parts":[[1998,1,1]]},"abstract":"<jats:p>Haqq, Christopher M., and Patricia K. Donahoe. Regulation of Sexual Dimorphism in Mammals. Physiol. Rev. 78: 1\u201333, 1998. \u2014 Sexual dimorphism in humans has been the subject of wonder for centuries. In 355 BC, Aristotle postulated that sexual dimorphism arose from differences in the heat of semen at the time of copulation. In his scheme, hot semen generated males, whereas cold semen made females (Jacquart, D., and C. Thomasset. Sexuality and Medicine in the Middle Ages, 1988). In medieval times, there was great controversy about the existence of a female pope, who may have in fact had an intersex phenotype (New, M.\u2009I., and E.\u2009S. Kitzinger. J. Clin. Endocrinol. Metab. 76: 3\u201313, 1993.). Recent years have seen a resurgence of interest in mechanisms controlling sexual differentiation in mammals. Sex differentiation relies on establishment of chromosomal sex at fertilization, followed by the differentiation of gonads, and ultimately the establishment of phenotypic sex in its final form at puberty. Each event in sex determination depends on the preceding event, and normally, chromosomal, gonadal, and somatic sex all agree. There are, however, instances where chromosomal, gonadal, or somatic sex do not agree, and sexual differentiation is ambiguous, with male and female characteristics combined in a single individual. In humans, well-characterized patients are 46, XY women who have the syndrome of pure gonadal dysgenesis, and a subset of true hermaphrodites are phenotypic men with a 46, XX karyotype. Analysis of such individuals has permitted identification of some of the molecules involved in sex determination, including SRY (sex-determining region Y gene), which is a Y chromosomal gene fulfilling the genetic and conceptual requirements of a testis-determining factor. The purpose of this review is to summarize the molecular basis for syndromes of sexual ambiguity seen in human patients and to identify areas where further research is needed. Understanding how sex-specific gene activity is orchestrated may provide insight into the molecular basis of other cell fate decisions during development which, in turn, may lead to an understanding of aberrant cell fate decisions made in patients with birth defects and during neoplastic change.<\/jats:p>","DOI":"10.1152\/physrev.1998.78.1.1","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T22:56:01Z","timestamp":1514156161000},"page":"1-33","source":"Crossref","is-referenced-by-count":75,"title":["Regulation of Sexual Dimorphism in Mammals"],"prefix":"10.1152","volume":"78","author":[{"given":"CHRISTOPHER M.","family":"HAQQ","sequence":"first","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, and Department of Genetics and Surgery, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PATRICIA K.","family":"DONAHOE","sequence":"additional","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, and Department of Genetics and Surgery, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00196234"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.6.785"},{"key":"B3","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1093\/genetics\/6.6.554","volume":"6","author":"AIDA T.","year":"1921","journal-title":"Genetics"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/endo-124-6-3089"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240480204"},{"key":"B5a","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1981.tb00305.x"},{"key":"B6","first-page":"736","volume":"32","author":"ALVESALO L.","year":"1980","journal-title":"Am. 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