{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:00:21Z","timestamp":1761764421946},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":4631,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[1992,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>During embryogenesis normal male phenotypic development requires the action of M\u00fcllerian Inhibiting Substance (MIS) which is secreted by Sertoli cells of the fetal testis. As testes differentiate in genetic (XY) males, they produce MIS which causes regression of the M\u00fcllerian ducts, the anlagen of the female reproductive tract. Soon thereafter, testicular androgens stimulate the Wolffian ducts. In females, on the other hand, MIS is not produced by grandulosa cells until after birth, before which, estrogens induce M\u00fcllerian duct development, while the Wolffian ducts passively atrophy in the absence of androgenic stimulation. High serum MIS levels in males are maintained until puberty, whereupon they fall to baseline levels. In females MIS is undetectable in serum until the peripubertal period when values approach the baseline levels of males. This distinct pattern of sexual and ontogenic expression presupposes and requires tight regulation.<\/jats:p><jats:p>MIS may play a role in gonadal function and development. Our laboratory has shown that an important role for ovarian MIS is to inhibit oocyte meiosis, perhaps providing maximal oocyte maturation prior to selection for ovulation and subsequent fertilization. Furthermore, Vigier et al. (Development 100:43\u201355) have recently obtained evidence that MIS may influence testicular differentiation, coincident with inhibition of aromatase activity. Current structure\u2010function studies demonstrate that MIS, like other growth regulators in its protein family, requires proteolytic cleavage to exhibit full biological activity. MIS can be inhibited by epidermal growth factor. This antagonism, which is common to all MIS functions so far investigated, is associated with inhibition of EGF receptor autophosphorylation. We have provided evidence that bovine MIS can inhibit female reproductive tract tumors arising in adults. More recent work with highly purified recombinant human MIS (rhMIS) has extended these early observations, showing that this recombinantly made fetal inhibitor can also suppress tumors of M\u00fcllerian duct origin and thus may prove to be useful in the clinical management of gynecologic neoplasms. Recent investigations have identified ocular melanoma as another potential target for rhMIS therapy in humans. \u00a9 1992 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mrd.1080320213","type":"journal-article","created":{"date-parts":[[2005,2,24]],"date-time":"2005-02-24T00:11:44Z","timestamp":1109203904000},"page":"168-172","source":"Crossref","is-referenced-by-count":17,"title":["M\u00fcllerian inhibiting substance in reproduction and cancer"],"prefix":"10.1002","volume":"32","author":[{"given":"Patricia K.","family":"Donahoe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90098-6"},{"key":"e_1_2_1_3_1","first-page":"281","article-title":"Growth of human tumor xenografts implanted under the renal capsule of normal immunocompetent mice","volume":"47","author":"Bogden AZ","year":"1979","journal-title":"Exp Cell Biol"},{"key":"e_1_2_1_4_1","first-page":"179","volume-title":"Handbook of Experimental Pharmacology","author":"Cate RL","year":"1990"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90783-X"},{"key":"e_1_2_1_6_1","unstructured":"CatlinEA EzzellR DonahoePK ManganaroT EbbRG MacLaughlinDT(1992):M\u00fcllerian inhibiting substance binding protein localization. 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Endocrinology in press.","DOI":"10.1210\/endo.130.2.1346380"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/321779a0"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90073-8"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","unstructured":"MacLaughlinDT HudsonPL GracianoAL KenneallyMK RaginRC ManganaroTF DonahoePK(1992):M\u00fcllerian duct regression and anti\u2010proliferative bioactivities of M\u00fcllerian Inhibiting Substance resides in its carboxy\u2010terminal domain. Endocrinology in press.","DOI":"10.1210\/endo.131.1.1612008"},{"key":"e_1_2_1_28_1","doi-asserted-by":"crossref","unstructured":"MacLaughlinDT LevinRK CatlinEA TaylorLA PrefferFI DonahoePK(1992):Identification of M\u00fcllerian Inhibiting Substance Specific Binding in Human Cell Lines. 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