Sex-specific Fetal Lung Development and Müllerian Inhibiting Substance

Catlin, Elizabeth A.; Powell, Susan M.; Manganaro, Thomas F.; Hudson, Peter; Ragin, Richard C.; Epstein, J.; Donahoe, Patricia K.

doi:10.1164/ajrccm/141.2.466

Cited by 69 publications

(35 citation statements)

References 5 publications

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“…MIS is a negative regulatory factor in fetal rat lung maturation, where it inhibits the production of pulmonary surfactant both in vitro and in vivo (12,13). MIS also inhibits oocyte meiosis in vitro (14,15).…”

Section: Mismentioning

confidence: 99%

Müllerian Inhibiting Substance Inhibits Breast Cancer Cell Growth through an NFκB-mediated Pathway

Segev¹,

Ha²,

Tran³

et al. 2000

Journal of Biological Chemistry

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130

117

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Mü llerian inhibiting substance (MIS), MIS,1 a member of the TGF-␤ family of hormones, causes regression of the epithelial-mesenchymal unit of the Mü llerian duct in the embryonic male urogenital ridge. In females the Mü llerian duct autonomously differentiates into the uterus, Fallopian tubes, and upper vagina (1). The Mü llerian ducts of both male and female embryos are responsive to MIS only during a critical period in development after which they lose sensitivity (1, 2). However, MIS is produced at high levels by Sertoli cells of the testis even after the regression of the Mü llerian duct, decreases at adolescence, and is produced throughout adult life. In females, it is synthesized by postnatal granulosa cells of the ovary and can be detected in the female serum until menopause (3, 4). Cleavage of MIS by a kex-like enzyme is required to manifest MIS activity since a noncleavable mutant is devoid of biological function (5).The MIS type II receptor gene, a highly conserved single transmembrane serine threonine kinase that is homologous to members of the TGF-␤ family of type II receptors, encodes a 2.0-kilobase mRNA (6 -8). It is expressed at high levels in the Mü llerian duct, Sertoli cells, and granulosa cells of the embryonic and adult gonads and in the uterus (8). The developmental significance of the MIS type II receptor was demonstrated in MIS type II receptor null male mice, which develop normally but have a persistent Mü llerian duct that forms a uterus and oviducts; this phenotype resembles that of MIS ligand-deficient mice (9 -11). Female MIS type II receptor or MIS ligand-deficient mice are normal and fertile as young adults.The detection of MIS in the serum of males and females even after the regression and differentiation of the Mü llerian duct (3, 4) suggests that MIS might be a multifunctional hormone. MIS is a negative regulatory factor in fetal rat lung maturation, where it inhibits the production of pulmonary surfactant both in vitro and in vivo (12, 13). MIS also inhibits oocyte meiosis in vitro (14,15). The presence of MIS type II receptor in non-Mü llerian tissues such as the ovary, lung, and Leydig cells of the testis (16 -18) and the occurrence of Leydig cell hyperplasia and Leydig cell tumors in receptor null male mice (11) also suggest that the biological action of MIS is not limited to the Mü llerian duct. Furthermore, MIS has been shown to inhibit the growth of tumor cells in vitro and in vivo (19 -22). Masiakos et al. (17), using ovarian epithelial cells derived from the ascites of ovarian cancer patients, correlated MIS type II receptor expression with MIS-mediated growth inhibition. Furthermore, exogenous MIS has been shown to inhibit metastases of the ocular melanoma cell line OM431 (23) and to block the growth of the vulvar epidermoid carcinoma cell line A431 and the OM431 cell line in vivo (21,24).Expression of MIS-related proteins including TGF-␤, activin, inhibin, and BMP ligands and their receptors has been demonstrated in human breast cancer cell lines and in breast cancer ...

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Section: Mismentioning

confidence: 99%

Müllerian Inhibiting Substance Inhibits Breast Cancer Cell Growth through an NFκB-mediated Pathway

Segev¹,

Ha²,

Tran³

et al. 2000

Journal of Biological Chemistry

Self Cite

130

117

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“…The importance of defining and ultimately purifying and sequencing the MIS receptor is twofold: 1) the developmentally precise, sexspecific growth control achieved by MIS at the Mullerian duct can then be more fully understood, and 2) the presence of MIS receptor in reproductive tract tumors of Mullerian duct origin may newly define a group of MIS responsive cancers. We hypothesized that if MIS exists as a ligand for its own receptor, then the MIS receptor should be present in MIS responsive tissue other than the urogenital ridge, specifically, fetal rat lung (Catlin et al, 1988(Catlin et al, , 1990(Catlin et al, , 1991. We therefore studied MIS binding and localization in vitro with time course experiments in the urogenital ridge, fetal lung, and control fetal tissues including the testis using laser confocal microscopy.…”

Section: Introductionmentioning

confidence: 99%

Mullerian inhibiting substance binding and uptake

Catlin

Ezzell

Donahoe

et al. 1992

Developmental Dynamics

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Mullerian inhibiting substance (MIS) is a 140,000 M, Sertoli cell derived glycoprokin with a critical regulatory role in the male fetus initiated presumably by ligand binding with receptor. To localize this binding species we performed time course incubations of cultured fetal rat lungs or control tissues with MIS, applied rabbit anti-MIS IgG, and fluorescein conjugated antirabbit IgG, and examined specimens with laser confocal microscopy. Punctate surface fluorescence followed by cytosolic and nuclear localization in lung consistent with specific adsorptive endocytosis was seen. Confocal imaging also detected MIS binding to the Mullerian duct in the urogenital ridge. Crosslinking of lZ5I-MIS with plasma membranes revealed a high molecular mass binder with signal displaceable by excess unlabeled ligand. These data support the hypothesis that a specific plasma membrane binding protein for MIS exists. o 1992 Wiley-Liss, Inc.

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“…There are some clues as to why preterm boys fare worse than preterm girls as advanced lung maturity by approximately 1 wk is reported in girls during the last 2 mo of pregnancy (9). Furthermore, male fetuses are exposed to higher levels of androgen and Mullerian inhibiting substance, which adversely affect surfactant production (10,11). Thus, it is reasonable to conclude that lung immaturity in premature boys contributes to their poorer outcomes.…”

mentioning

confidence: 99%