Mario Ascoli, PhD

Portrait
Professor of Pharmacology
Professor of Obstetrics and Gynecology

Contact Information

Primary Office: 2-530 BSB
51 Newton Rd.
Iowa City, IA 52242
319-335-9907

Lab: 2-505 BSB
Iowa City, IA 52242
319-335-9933

Education

BS, Biochemistry, San Carlos University
PhD, Biochemistry, Vanderbilt University

Postdoctoral Fellow, Department of Biochemistry, M.D. Anderson Hospital and Tumor Institute, The University of Texas, Houston, TX

Research Summary

Receptors and Signal Transduction / Cellular and Molecular Endocrinology The lutropin/choriogonadotropin (LHR) and follitropin (FSHR) receptors are the principal regulators of reproduction in humans. Loss-of-function and gain-of-function mutations of these receptors are known to be associated with a number of disorders of the reproductive system such as ovarian dysgenesis, ovarian hyperstimulation syndrome, Leydig cell hypoplasia, male-limited precocious puberty and Leydig cell tumors. The cognate hormones, lutropin/choriogonadotropin (LH/CG) and follitropin are widely used in the treatment of infertility. Research in my laboratory is driven by the hypothesis that the binding of agonist to the LHR and the FSHR result in the activation of multiple signaling pathways, and that these pathways, either alone or in combination, stimulate the proliferation and differentiated functions of their respective target cells (Leydig and Granulosa cells). Some of the projects that we are currently working on are as follows. (1) Examine the involvement of G protein-dependent and G protein-independent pathways on the LHR and FSHR-induced activation of mitogenic signaling cascades. (2) Characterize the involvement of the MEK/ERK signaling cascades on the proliferation and differentiation of Leydig cells. (3) Characterize the involvement of Gq/11 cascades on the actions of LHR in the ovary. Experimental systems used in my laboratory include a Leydig tumor cell line, primary cultures of granulosa or Leydig cells and mice with target cell specific deletions of MEK or Gq/11.

Publications

Kapfhamer, J., Waite, C. & Ascoli, M. (2017). The Ga<sub>q/11</sub>-provoked induction of Akr1c18 in murine luteal cells is mediated by phospholipase C. Molecular and cellular endocrinology. PMID: 29107092.

Waite, C., Mejia, R. & Ascoli, M. (2016). Gq/11-dependent changes in the murine ovarian transcriptome at the end of gestation. Biology Reproduction, 94(3), 1-12. PMID: 26843449.

Ascoli, M., Mebane, D. & Fazleabas, A. T. (2016). Frontiers in Reproduction (FIR): An Assessment of Success. Biology Reproduction, 95(1), 27, 1-6. PMID: 27335071.

Cookingham, L. M., Van Voorhis, B. J. & Ascoli, M. (2015). Do alterations in follicular fluid proteases contribute to human infertility?. J Assist Reprod Genet, 32(5), 737-45. PMID: 25682117.

Mejia, R., Waite, C. & Ascoli, M. (2015). Activation of Gq/11 in the mouse corpus luteum is required for parturition. Mol Endocrinol, 29(2), 238-46.

Breen, S. M., Andric, N., Tai, P., Xie, F., Offermans, S., Gossen, J. A. & Ascoli, M. (2013). Ovulation involves the luteinizing hormone-dependent activation of Gq/11 in granulosa cells. Mol Endocrinol, 27, 1483-1491.

Matzkin, M. E., yamashita, S. & Ascoli, M. (2013). The ERK1/2 pathway regulates testosterone synthesis by coordinately regulating the expression of steroidogenic genes in Leydig cells. Mol Cell Endocrinol., 370(1-2), 130-137.

Kim, J., Stirling, K., Cooper, M. E., Ascoli, M., Momany, A. M., McDonald, E. L., Ryckman, K. K., Rhea, L., Schaa, K. L., Cosentino, V., Gadow, E., Saleme, C., Shi, M., hallman, M., Plunket, J., Teramo, K. A., Muglia, L. J., Feenstra, B., Boyd, H. A., Melbye, M., Marazita, M. L., Dagle, J. M. & Murray, J. C. (2013). Sequence variants in oxytocin pathway gnees and preterm birth: A candidate gene association study. BMC Med Genet, 14:77. DOI: 10.1186/1471-2350-14-77.

Ascoli, M., Narayan, P. (2013). The gonadotropin hormones and their receptors. In , J. Strauss , R. Barbieri (Eds.) In Yen and Jaffe’s Reproductive Endocrinology: Physiology, Pathophysiology and Clinical Management, 7th Edition. pp. 27-44. Saunders/Elsevier, Philadelphia, PA.

Yamashita, S., Tai, P., Charron, J., Ko, C. & Ascoli, M. (2011). The Leydig cell MEK/ERK pathway is critical for maintaining a functional population of adult Leydig cells and for fertility. Mol Endocrinol, 25(7), 1211-1222.

Tai, P., Ascoli, M. (2011). Reactive oxygen species (ROS) play a critical role in the cAMP-induced activation of Ras and the phosphorylation of ERK1/2 in Leydig cells. Mol Endocrinol, 25(5), 885-893.

Andric, N., Thomas, M. & Ascoli, M. (2010). Transactivation of the epidermal growth factor receptor is involved in the lutropin receptor-mediated down-regulation of ovarian aromatase expression in vivo. Mol Endocrinol, 24(3), 552-560.

Tai, P., Shiraishi, K. & Ascoli, M. (2009). Activation of the lutropin/choriogonadotropin receptor inhibits apoptosis of immature Leydig cells in primary culture. Endocrinology, 150(8), 3766-3773.

Ascoli, M., Puett, D. (2009). The gonadotropin hormones and their receptors. In J. Strauss , R. Barbieri (Eds.) In Yen and Jaffe’s Reproductive Endocrinology: Physiology, Pathophysiology and Clinical Management, 6th Edition. pp. 35-55. Saunders/Elsevier, Philadelphia, PA.

Galet, C., Ascoli, M. (2008). Arrestin-3 is essential for the activation of Fyn by the luteinizing hormone receptor (LHR) in MA-10 cells. Cell Signal, 20(10), 1822-1829.

Andric, N., Ascoli, M. (2008). The luteinizing hormone receptor-activated extracellularly regulated kinase-1/2 cascade stimulates epiregulin release from granulosa cells. Endocrinology, 149(11), 5549-5556.

Shiraishi, K., Ascoli, M. (2008). A co-culture system reveals the involvement of intercellular pathways as mediators of the lutropin receptor (LHR)-stimulated ERK1/2 phosphorylation in Leydig cells. Exp Cell Res, 314(1), 25-37.

Andric, N., Ascoli, M. (2008). Mutations of the lutropin/choriogonadotropin receptor that do not activate the phosphoinositide cascade allow hCG to induce aromatase expression in immature rat granulosa cells. Mol Cell Endocrinol, 285(1-2), 62-72.

Ascoli, M. (2007). Potential mitogenic signals generated by the wild-type and constitutively active mutants of the lutropin/choriogonadotropin receptor (LHR). Mol Cell Endocrinology, 260-262, 244-248.

Ascoli, M. (2007). Inmortalized Leydig cell lines as models for studying Leydig cell physiology. Humana Press, 373-381.

Shiraishi, K., Ascoli, M. (2007). Lutropin/choriogonadotropin stimulate the proliferation of primary cultures of rat Leydig cells through a pathway that involves activation of the extracellularly regulated kinase 1/2 cascade. Endocrinology, 148(7), 3214-3225.

Mizutani, T., Shiraishi, K., Welsh, T. & Ascoli, M. (2006). Activation of the Lutropin/choriogonadotropin receptor (LHR) in MA-10 cells leads to the tyrosine phosphorylation of the focal adhesion kinase (FAK) by a pathway that involves Src family kinases. Mol Endocrinology, 20(3), 619-630.

Shiraishi, K., Ascoli, M. (2006). Activation of the lutropin/choriogonadotropin receptor (LHR) in MA-10 cells stimulates tyrosine kinase cascades that activate Ras and the extracellular signal regulated kinases (ERK1/2). Endocrinology, 147(7), 3419-3427.

Andric, N., Ascoli, M. (2006). A delayed, gonadotropin dependent and growth-factor mediated activation of the ERK1/2 cascade negatively regulates aromatase expression in granulosa cells. Mol Endocrinology, 20(12), 3308-3320.

Galet, C., Ascoli, M. (2006). A constitutively active mutant of the human lutropin receptor (hLHR-L457R) escapes lysosomal targeting and degradation. Mol Endocrinology, 20(11), 2931-2945.

Ascoli, M. (2005). Learning new tricks from an old dog: the processing of the intracellular precursor of the luteinizing hormone receptor (LHR) into the mature cell-surface LHR is a regulated process. (Vols. 146). pp. 3221-3223. Endocrinology.

Donadeu, F. X., Ascoli, M. (2005). The differential effects of the gonadotropin receptors on aromatase expression in primary cultures of immature rat granulosa cells are highly dependent on the density of receptors expressed and the activation of the inositol phosphate cascade. Endocrinology, 146(9), 3907-3916.

Bhaskaran, R. S., Ascoli, M. (2005). The postendocytotic fate of the gonadotropin receptors is an important determinant of the desensitization of gonadotropin responses. J Mol Endocrinology, 34(2), 447-457. PMID: 15821109.

Galet, C., Ascoli, M. (2005). The differential binding affinities of the lutropin/choriogonadotropin receptor (LHR) for lutropin (LH) and choriogonadotropin (CG) are dictated by different extracellular domain residues. Mol Endocrinology, 19(5), 1263-1276. PMID: 15677709.

Mizrahi, D., Ascoli, M. & Segaloff, D. L. (2004). The Thyroid-Stimulating Hormone/Luteinizing Hormone/Follicle-Stimulating Hormone Receptors. Elsevier Science, 3, 180-186.

Galet, C., Hirakawa, T. & Ascoli, M. (2004). The postendocytotic trafficking of the hLHR is mediated by a transferable motif consisting of the C-terminal cysteine and an upstream leucine. Mol Endocrinology, 18(2), 434-446. PMID: 14605099.

Krishnamurth, H., Galet, C. & Ascoli, M. (2003). The association of arrestin-3 with the follitropin receptor depends on receptor activation and phosphorylation. Mol Cell Endocrinology, 204(1-2), 127-140. PMID: 12850288.

Galet, C., Min, L., Narayanan, R., Kishi, M., Weigel, N. L. & Ascoli, M. (2003). Identification of a transferable two amino acid motif (GT) present in the C-terminal tail of the human lutropin receptor that redirects internalized G protein-coupled receptors from a degradation to a recycling pathway. Mol Endocrinology, 17(3), 411-422. PMID: 12554787.

Hirakawa, H., Ascoli, M. (2003). A constitutively active somatic mutation of the human lutropin receptor found in Leydig tumors activates the same families of G proteins as germ line mutations associated with Leydig cell hyperplasia. Endocrinology, 144(9), 3872-3878. PMID: 12933660.

Hirakawa, T., Ascoli, M. (2003). The lutropin/choriogonadotropin receptor (LHR)-induced phosphorylation of the extracellular regulated kinases (ERKs) in Leydig cells is mediated by a protein kinase A-dependent activation of Ras. Mol Endocrinology, 17(11), 2189-2200. PMID: 1290236.

Hirakawa, T., Galet, C., Kishi, M. & Ascoli, M. (2003). GIPC binds to the human lutropin receptor (LHR) through an unusual PDZ domain binding motif and it regulates the sorting of the internalized human choriogonadotropin (hCG) and the density of cell surface LHR. J Biol Chem, 278(49), 49348-49357. PMID: 14507927.

Bhaskaran, R. S., Min, L., Krishnamurty, H. & Ascoli, M. (2003). Studies with chimeras of the gonadotropin receptors reveal the importance of third intracellular loop threonines on the formation of the receptor/non-visual arrestin complex. Biochemistry, 42(47), 13950-13959. PMID: 14636063.

Krishnamurty, H., Kishi, H., Shi, M., Galet, C., Bhaskaran, R. S., Hirakawa, T. & Ascoli, M. (2003). Post-endocytotic trafficking of the FSH/FSH receptor complex. Mol Endocrinol, 17(11), 2162-2176. PMID: 12907758.

Ascoli, M., Fanelli, F. & Segaloff, D. L. (2002). The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocrine Reviews, 23, 141-174.

Min, L., Galet, C. & Ascoli, M. (2002). The association of arrestin-3 with the human lutropin/choriogonadotropin receptor depends mostly on receptor activation rather than on receptor phosphorylation. J Biol Chem, 277(1), 702-710. PMID: 11696538.

Kishi, H., Krishnamurty, H., Galet, C., Baskaran, R. S. & Ascoli, M. (2002). Identification of a short linear sequence present in the C-terminal tail of the rat follitropin receptor that modulates arrestin-3 binding in a phosphorylation-independent fashion. J Biol Chem, 277(24), 21939-21946. PMID: 11934883.

Hirakawa, T., Galet, C. & Ascoli, M. (2002). MA-10 cells transfected with the human lutropin/choriogonadotropin receptor (hLHR): a novel experimental paradigm to study the functional properties of the hLHR. Endocrinology, 143(3), 1026-1035. PMID: 11861529.

Li, S., Liu, X. & Ascoli, M. (2001). Mutations of the second extracellular loop of the human lutropin receptor emphasize the importance of receptor activation and de-emphasize the importance of receptor phosphorylation in agonist-induced internalization. J Biol Chem, 276(11), 7986-7973. PMID: 11118455.

Kishi, M., Liu, X., Hirakawa, T., Reczek, D., Bretscher, A. & Ascoli, M. (2001). Identification of two distinct structural motifs that, when added to the C-terminal tail of the rat lutropin receptor, redirect the internalized hormone-receptor complex from a degradation to a recycling pathway. Mol Endocrinology, 15, 1624-1635. PMID: 11518811.

Li, S., Liu, X. & Ascoli, M. (2000). p38JAB1 binds to the intracellular precursor of the lutropin/choriogonadotropin receptor and promotes its degradation. J Biol Chem, 275, 13386-13393. PMID: 10788448.

Nakamura, K., Liu, X. & Ascoli, M. (2000). Seven non-contiguous intracellular residues of the lutropin/choriogonadotropin receptor dictate the rate of agonist-induced internalization and its sensitivity to non-visual arrestins. J Biol Chem, 245, 241-247. PMID: 10617611.

Kishi, M., Ascoli, M. (2000). The C-terminal tail of the rat lutropin/choriogonadotropin receptor independently modulates hCG-induced internalization of the cell surface receptor and the lysosomal targeting of the internalized hCG-receptor complex. Mol Endocrinology, 14(6), 926-936. PMID: 10847593.

Min, L., Ascoli, M. (2000). Effect of activating and inactivating mutations on the phosphorylation and trafficking of human lutropin/choriogonadotropin receptor. Mol Endocrinology, 14(11), 1797-1810. PMID: 11075813.

Kishi, H., Ascoli, M. (2000). Multiple distant amino acid residues present in the serpentine region of the follitropin receptor modulate the rate of agonist-induced internalization. J Biol Chem, 275(40), 31030-31037. PMID: 10915803.

Nakamura, K., Liu, X. & Ascoli, M. (1999). The rate of internalization of the gonadotropin receptors is greatly affected by the origin of the extracellular domain. J Biol Chem, 274, 25426-25432. PMID: 10464272.

Nakamura, K., Lazari, M., Li, S., Korgaonkar, C. & Ascoli, M. (1999). Role of the rate of internalization of the agonist-receptor complex on the agonist-induced down-regulation of the lutropin-choriogonadotropin receptor. Mol Endocrinol, 13, 1295-1304. PMID: 10446904.

Nakamura, K., Ascoli, M. (1999). A dileucine-based motif in the C-terminal tail of the lutropin/choriogonadotropin receptor inhibits endocytosis of the agonist-receptor complex. Mol Pharmacol, 56, 728-736. PMID: 10496955.

Lazari, M., Liu, X., Benovic, J. L. & Ascoli, M. (1999). Role of G protein-coupled receptor kinases on the agonist-induced phosphorylation and internalization of the follitropin receptor. Mol Endocrinol, 13, 866-878. PMID: 10379886.

Nakamura, K., Hipkin, R. W. & Ascoli, M. (1998). The agonist-induced phosphorylation of the rat follitropin receptor (rFSHR) maps to the first and third intracellular loops. Mol Endocrinol, 12, 580-591. PMID: 9544993.

Fabritz, J., Ryan, S. & Ascoli, M. (1998). Transfected cells express mostly the intracellular precursor of the lutropin/choriogonadotropin receptor but this precursor binds choriogonadotropin with high affinity. Biochemistry, 37, 664-672. PMID: 9425089.

Nakamura, K., Krupnick, J. G., Benovic, J. L. & Ascoli, M. (1998). Signaling and phosphorylation-impaired mutants of the rat follitropin receptor reveal an activation- and phosphorylation-independent but arrestin-dependent pathway for internalization. J Biol Chem, 273, 24346-24354. PMID: 9733722.

Lazari, M., Bertrand, J., Nakamura, K., Liu, X., Krupnick, J. G., Benovic, J. L. & Ascoli, M. (1998). Mutation of individual serine residues in the C-terminal tail of the lutropin/choriogonadotropin receptor reveal distinct structural requirements for agonist-induced uncoupling and agonist-induced internalization. J Biol Chem, 273, 18316-18324. PMID: 9660797.

Min, K. S., Liu, X., Fabritz, J. J., Abell, A. N. & Ascoli, M. (1998). Mutations that induce constitutive activation and mutations that impair signal transduction modulate the basal and/or agonist-stimulated internalization of the lutropin/choriogonadotropin receptor. J Biol Chem, 273, 34911-34919. PMID: 9857020.

Ascoli, M. (1997). Molecular basis of the regulation of the lutropin/chorio-gonadotropin (LH/CG) receptor. Biochem Soc Transactions, 25, 943-948.

Wang, Z., Liu, X. & Ascoli, M. (1997). Phosphorylation of the lutropin/ choriogonadotropin receptor facilities uncoupling of the receptor from adenylyl cyclase and endocytosis of the bound hormone. Mol Endocrinol, 11, 183-192. DOI: 10.1210/mend.11.2.9889.

Dhanwada, K. R., Vijapurkar, U. & Ascoli, M. (1996). Two mutations of the lutropin/choriogonadotropin receptor that impair signal transduction also interfere with receptor-mediated endocytosis. Mol Endocrinol, 10, 544-554. PMID: 8732685.

Ascoli, M. (1996). Functional consequences of the phosphorylation of the gonadotropin receptors. Biochemical Pharmacology, 52, 1647-1655.

Wang, Z., Hipkin, R. W. & Ascoli, M. (1996). Progressive cytoplasmic truncation of the lutropin-choriogonadotropin receptor prevent agonist- or phorbol ester-induced phosphorylation, impair agonist- or phorbol ester-induced desensitization, and enhance agonist-induced receptor down-regulation. Mol Endocrinol, 10, 748-758. PMID: 8776735.

Hoelscher, S. R., Ascoli, M. (1996). Immortalized Leydig cell lines as models for studying Leydig cell physiology. Cache River Press, 523-534.

Zhu, H., Wang, H. & Ascoli, M. (1995). The lutropin/choriogonadotropin (LH/CG) receptor is palmitoylated at intracellular cysteine residues. Mol Endocrinol, 9, 141-150. PMID: 7776964.

Hipkin, R. W., Liu, X. & Ascoli, M. (1995). Truncation of the C-terminal tail of the follitropin (FSH) receptor does not impair the agonist- or phorbol ester-induced receptor phosphorylation and uncoupling. J Biol Chem, 270, 26683-26689. PMID: 7592895.

Hipkin, R. W., Wang, Z. & Ascoli, M. (1995). Human chorionic gonadotropin- and phorbol ester-stimulated phosphorylation of the LH/CG receptor maps to serines 635, 639, 652 in the C-terminal cytoplasmic tail. Mol Endocrinol, 9, 151-158. PMID: 7776965.

Hoelscher, S. R., Ascoli, M. (1995). Decreased stathmin expression does not affect the actions of human choriogonadotropin or epidermal growth factor in Leydig tumor cells. Endocrinology, 136, 5004-5013. PMID: 7588235.

Ascoli, M., Segaloff, D. L. (1995). Adenohypophyseal hormones and related substances. In J. G. Hardman , L. E. Limbird (Eds.) In Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th Edition. pp. 1363-1382. McGraw-Hill, Inc., New York, NY.

Hoelscher, S. R., Ascoli, M. (1994). Leydig tumor cell protein phosphorylated in response to stimulation with choriogonadotropin or epidermal growth factor is identified as stathmin. Endocrinology, 135, 662-666. PMID: 8033814.

Quintana, J., Hipkin, R. W., Sanchez-Yague, J. & Ascoli, M. (1994). Follitropin (FSH) and a phorbol ester stimulate the phosphorylation of the FSH receptor in intact cells. J Biol Chem, 269, 8772-8779. PMID: 8132609.

Nelson, S., Liu, X., Noblett, L., Fabritz, J. & Ascoli, M. (1994). Characterization of the functional properties of nuclear binding proteins of the rat luteinizing hormone/chorionic gonadotropin (LH/CG) receptor promoter in Leydig cells. Endocrinology, 135, 1729-1739. PMID: 7956896.

Hipkin, R. W., Sanchez-Yague, J. & Ascoli, M. (1993). Agonist-induced phosphorylation of the luteinizing hormone chorionic gonadotropin (LH/CG) receptor expressed in a stably transfected cell line. Mol Endocrinol, 7, 823-832.

Sanchez-Yague, J., Hipkin, R. W. & Ascoli, M. (1993). Biochemical properties of the agonist-induced desensitization of the follicle-stimulating hormone and luteinizing hormone/chorionic gonadotropin-responsive adenylyl cyclase in cells expressing the recombinant gonadotropin receptors. Endocrinol, 132, 1007-1016.

Quintana, J., Hipkin, R. W. & Ascoli, M. (1993). A polyclonal antibody to a synthetic peptide derived from the rat FSH receptor reveals the recombinant receptor as a 74kDa protein. Endocrinology, 133, 2098-2104.

Wang, Z., Wang, H. & Ascoli, M. (1993). Mutation of a highly conserved acidic residue present in the second intracellular loop of G protein-coupled receptors does not impair hormone binding or signal transduction of the LH/CG receptor. Mol Endocrinol, 7, 85-93. PMID: 8383288.

Quintana, J., Wang, H. & Ascoli, M. (1993). The regulation of the binding affinity of the luteinizing hormone/choriogonadotropin receptor by sodium ions is mediated by a highly conserved aspartate located in the second transmembrane domain of G protein-coupled receptors. Mol Endocrinol, 7, 767-775. PMID: 8395653.

Hoelscher, S. R., Ascoli, M. (1993). Identification of a Leydig tumor cell protein that is phosphorylated in response to stimulation with choriogonadotropin or epidermal growth factor. Endocrinol, 132, 2229-2238. PMID: 8477667.

Segaloff, D. L., Ascoli, M. (1993). The lutropin/choriogonadotropin (LH/CG) receptor...4 years later. Endocrine Reviews, 14, 324-347.

Stocco, D. M., Ascoli, M. (1993). The use of genetic manipulation of MA-10 Leydig tumor cells to demonstrate the role of mitochondrial proteins in the acute regulation of steroidogenesis. Endocrinology, 132, 959-967. PMID: 8382603.

Nelson, S., Ascoli, M. (1992). Epidermal growth factor, a phorbol ester and cAMP decrease the transcription of the LH/CG receptor gene in MA-10 Leydig tumor cells. Endocrinology, 131, 615-620.

Hipkin, R. W., Sanchez-Yague, J. & Ascoli, M. (1992). Identification and characterization of an LH/CG receptor precursor in a human kidney cell line stably transfected with the rat luteal LH/CG receptor cDNA. Mol Endocrinol, 6, 2210-2218.

Sanchez-Yague, J., Rodriguez, M. C., Segaloff, D. L. & Ascoli, M. (1992). Truncation of the cytoplasmic tail of the lutropin-choriogonadotropin receptor prevents agonist-induced uncoupling. J Biol Chem, 267, 7217-7220.

Wang, H., Nelson, S., Ascoli, M. & Segaloff, D. L. (1992). The 5' flanking region of the rat-lutropin/choriogonadotropin receptor gene confers Leydig cell expression and negative regulation of gene transcription by cAMP. Mol Endocrinol, 6, 320-326.

Segaloff, D. L., Ascoli, M. (1992). The gonadotropin receptors: insights learned from cloning of their cDNA's. Oxford Reviews of Reproductive Biology, 14, 141-168.

Wang, H., Segaloff, D. L. & Ascoli, M. (1991). Lutropin/choriogonadotropin down-regulates its receptor by both receptor-mediated endocytosis and a cAMP-dependent reduction in receptor mRNA. J Biol Chem, 266, 780-785.

Wang, H., Segaloff, D. L. & Ascoli, M. (1991). Epidermal growth factor and phorbol esters reduce the levels of the cognate mRNA for the LH/CG receptor. Endocrinology, 128, 2651-2653.

Hoelscher, S. R., Sairam, M. R. & Ascoli, M. (1991). The slow rate of internalization of deglycosylated hCG is not due to its inability to stimulate cAMP accumulation. Endocrinology, 128, 2837-2843.

Wang, H., Ascoli, M. & Segaloff, D. L. (1991). Multiple lutropin/chorio-gonadotropin receptor mRNA transcripts. Endocrinology, 129, 133-138.

Swinnen, J. V., D'Souza, B., Conti, M. & Ascoli, M. (1991). Attenuation of cAMP-mediated responses in MA-10 Leydig tumor cells by genetic manipulation of a cAMP-phosphodiesterase. J Biol Chem, 266, 14383-14389.

Segaloff, D. L., Sprengel, R., Nickolics, K. & Ascoli, M. (1990). The structure of the LH/CG receptor. Recent Progress Hormone Res, 46, 261-303.

Pignataro, O. P., Ascoli, M. (1990). Studies with insulin and insulin-like growth factor-I show that the increased labeling of phosphatidylinositol-3,4-biphosphate is not sufficient to elicit the diverse actions of epidermal growth factor on MA-10 Leydig tumor cells. Mol Endocrinol, 4, 758-765.

Hafez, M. M., Ascoli, M. (1990). Epidermal growth factor desensitizes the gonadotropin-responsive adenylyl cyclase in membranes isolated from MA-10 Leydig tumor cells and luteinized rat ovaries. Endocrinology, 127, 394-402.

Wang, H., Ascoli, M. (1990). Reduced gonadotropin responses in a novel clonal strain of Leydig tumor cells established by transfection of MA-10 cells with a mutant gene of the type I regulatory subunit of the cAMP-dependent protein kinase. Mol Endocrinol, 4, 80-90.

Miller, E. S., Ascoli, M. (1990). Anti-phosphotyrosine immunoprecipitation of phosphatidylinositol 3' kinase activity in different cell types after exposure to epidermal growth factor. Biochem Biophys Res Comm, 173, 289-295.

Pignataro, O. P., Ascoli, M. (1990). Epidermal growth factor increases the labeling of phosphatidylinositol-3,4-bisphosphate in MA-10 Leydig tumor cells. J Biol Chem, 265, 1718-1723.

Ascoli, M., Pignataro, O. P. & Segaloff, D. L. (1989). The inositol phosphate/diacylglycerol pathway in MA-10 Leydig tumor cells. Activation by arginine vasopressin and lack of effect of epidermal growth factor and human choriogonadotropin. J Biol Chem, 264, 6674-6681.

Ascoli, M., Segaloff, D. L. (1989). Regulation of the differentiated function of Leydig tumor cells by epidermal growth factor. Ann. N.Y. Acad. Sci., 564, 99-115.

Ascoli, M. (1989). Quality versus quantity. (Vols. 124). (i-ii) Endocrinology.

Ascoli, M., Segaloff, D. L. (1989). On the structure of the LH/CG receptor. Endocrine Reviews, 10, 27-44.

Ascoli, M., Segaloff, D. L. (1988). Regulation of luteinizing hormone receptors and actions in Leydig tumor cells by epidermal growth factor. Raven Press, New York, 129-138.

Segaloff, D. L., Ascoli, M. (1988). Internalization of peptide hormones and hormone receptors. Elsevier Biomedical Press, Amsterdam,(part 1), 133-149.

Pereira, M. E., Segaloff, D. L. & Ascoli, M. (1988). Ca+2 is an inhibitor of adenylate cyclase in MA-10 Leydig tumor cells. Endocrinology, 122, 2232-2239.

Pereiera, M. E., Segaloff, D. L. & Ascoli, M. (1988). Inhibition of gonadotropin-responsive adenylate cyclase in MA-10 Leydig tumor cells by epidermal growth factor. J Biol Chem, 263, 9761-9766.

Rosemblit, N., Ascoli, M. & Segaloff, D. L. (1988). Characterization of an antiserum to the rat luteal LH/CG receptor. Endocrinology, 123, 2284-2290.

Pereira, M. E., Segaloff, D. L., Ascoli, M. & Eckstein, F. (1987). Inhibition of choriogonadotropin-activated steroidogenesis in cultured Leydig tumor cells by the Rp diastereoisomer of adenosine 3',5'-cyclic phosphorothioate. J Biol Chem, 262, 6093-6100.

Ascoli, M., Segaloff, D. L. (1987). On the fates of receptor-bound ovine luteinizing hormone and human chorionic gonadotropin in cultured Leydig tumor cells. Demonstration of similar rates of internalization. Endocrinology, 120, 1161-1172.

Kim, I., Ascoli, M. & Segaloff, D. L. (1987). Immunoprecipitation of the lutropin/choriogonadotropin receptor from biosynthetically labeled Leydig tumor cells. A 92-kDa glycoprotein. J Biol Chem, 262, 470-477.

Ascoli, M., Euffa, J. & Segaloff, D. L. (1987). Epidermal growth factor activates steroid biosynthesis in cultured Leydig tumor cells without affecting the levels of cAMP, and potentiates the activation of steroid biosynthesis by choriogonadotropin and cAMP. J Biol Chem, 262, 9296-9203.

Ascoli, M., Segaloff, D. L. (1986). Effects of "collagenase" on the structure of the lutropin/choriogonadotropin (LH/CG) receptor. J Biol Chem, 261, 3807-3815.

Ascoli, M., Freeman, D. A. (1985). Sources of cholesterol used for steroid biosynthesis in cultured Leydig tumor cells. The George F. Stickley Co., Philadelphia, 21-32.

Ascoli, M. (1985). Regulation of luteinizing hormone receptors and actions. CRC Press, Boca Raton, 199-217.

Ascoli, M. (1985). Luteinizing hormone action and receptors. M. Ascoli (Eds.) CRC Press, Boca Raton.

Pandey, K. N., Ascoli, M. & Inagami, T. (1985). Induction of renin activity by gonadotropin hormones in cultured Leydig tumor cells. Endocrinology, 117, 2120-2126.

Ascoli, M. (1985). Functions and regulation of cell surface receptors in cultured Leydig tumor cells. Academic Press, New York, 2, 368-400.

Ascoli, M., Freeman, D. A. (1984). Regulation of gonadotropin receptors and steroidogenic responses in cultured Leydig tumor cells. Plenum Press, New York, 1, 487-524.

Buettner, K., Ascoli, M. (1984). Na+ modulates the affinity of the lutropin/choriogonadotropin (LH/CG) receptor. J Biol Chem, 259, 15078-15084.

Ascoli, M. (1984). Lysosomal accumulation of the hormone-receptor complex during receptor-mediated endocytosis of human choriogonadotropin. J Cell Biol, 99, 1242-1250.

Freemean, D. A., Ascoli, M. (1983). The low density lipoprotein pathway of cultured Leydig tumor cells: utilization of low density lipoprotein-derived cholesterol for steroidogenesis. Biochem Biophys Acta, 754, 71-81.

Ascoli, M., Freeman, D. A., Sheets, J. J. & Vickery, L. E. (1983). Inhibition of steroidogenesis in cultured Leydig tumor cells by 22-amino-23,24-bisnor-5-cholen-3ß-ol and (20R)-20-phenyl-5-pregnene-3ß,20-diol. Endocrinology, 113, 127-132.

Lloyd, C. E., Ascoli, M. (1983). On the mechanisms involved in the regulation of the cell surface receptors for human choriogonadotropin and mouse epidermal growth factor in cultured Leydig tumor cells. J Cell Biol, 96, 521-526.

Ascoli, M. (1983). An improved method for the solubilization of stable gonadotropin receptors. Endocrinology, 113, 2129-2134.

Ascoli, M. (1982). Regulation of steroid production in gonadal, adrenal and placental tumor cells. Academic Press, New York, 409-444.

Freeman, D. A., Ascoli, M. (1982). Studies on the source of cholesterol used for steroid biosynthesis in cultured Leydig tumor cells. J Biol Chem, 257, 14231-14238.

Ascoli, M. (1982). Receptor-mediated uptake and degradation of human choriogo¬nadotropin: fate of the hormone subunits. Ann. N.Y. Acad. Sci, 383, 151-173.

Freeman, D. A., Ascoli, M. (1982). Desensitization of steroidogenesis in cultured Leydig tumor cells: role of cholesterol. Proc Natl Acad Sci (USA), 79, 7796-7800.

Ascoli, M. (1982). Internalization and degradation of receptor-bound human choriogonadotropin in Leydig tumor cells: fate of the hormone subunits. J Biol Chem, 257, 13306-13311.

Ascoli, M. (1981). Regulation of gonadotropin receptors and gonadotropin responses in a clonal strain of cultured Leydig tumor cells by epidermal growth factor. J Biol Chem, 256, 179-183.

Segaloff, D. L., Ascoli, M. (1981). Removal of surface-bound human choriogonadotropin results in cessation of hormonal responses in cultured Leydig tumor cells. J Biol Chem, 256, 11420-11423.

Segaloff, D. L., Puett, D. & Ascoli, M. (1981). The dynamics of the steroidogenic response of perifused Leydig tumor cells to human chorionic gonadotropin, ovine luteinizing hormone, cholera toxin and adenosine 3',5'-cyclic monophosphate. Endocrinology, 108, 632-638.

Ascoli, M. (1981). Effects of hypocholesterolemia and chronic hormonal stimulation on sterol and steroid metabolism in a Leydig cell tumor. J Lipid Res, 22, 1247-1253.

Ascoli, M. (1981). Degradation of receptor-bound human choriogonadotropin and activation of steroidogenesis in Leydig tumor cells. Academic Press, New York, 271-282.

Freemean, D. A., Ascoli, M. (1981). Desensitization to gonadotropins in cultured Leydig tumor cells involves both loss of gonadotropin receptors and decreased steroidogenic capacity. Proc Natl Acad Sci (USA), 78, 6309-6313.

Ascoli, M. (1981). Characterization of several clonal lines of cultured Leydig tumor cells: Gonadotropin receptors and steroidogenic responses. Endocrinology, 108, 88-95.

Bahn, R. S., Worsham, A., Ascoli, M. & Rabin, D. (1981). Characterization of steroid production in cultured human choriocarcinoma cells. J Clin Endocrinol Metab, 52, 447-450.

Segaloff, D. L., Ascoli, M. & Puett, D. (1981). Characterization of the desensitized state of Leydig tumor cells. Biochem Biophys Acta, 675, 351-358.

Alberet, D. H., Ascoli, M., Puett, D. & Coniglio, J. G. (1980). Lipid composition and gonadotropin-mediated lipid metabolism of the M5480 murine Leydig cell tumor. J Lipid Res, 21, 862-867.

Ascoli, M. (1980). Degradation of the subunits of receptor-bound human choriogonadotropin by Leydig tumor cells. Biochem Biophys Acta, 629, 409-417.

Bahn, R. S., Speeg Jr., K. V., Ascoli, M. & Rabin, D. (1980). Epidermal growth factor stimulates production of progesterone in cultured human choriocarcinoma cells. Endocrinology, 107, 2121-2123.

Ascoli, M. (1979). Inhibition of the degradation of receptor-bound human choriogonadotropin by leupeptin. Biochem Biophys Acta, 586, 608-614.

Lacroix, A., Ascoli, M., Puett, D. & McKenna, T. J. (1979). Steroidogenesis of hCG-responsive Leydig tumor variants. J Steroid Biochem, 10, 669-675.

Ascoli, M., Puett, D. (1978). Gonadotropin binding and stimulation of steroidogenesis in Leydig tumor cells. Proc Natl Acad Sci (USA), 75, 99-102.

Ascoli, M., Puett, D. (1978). Inhibition of the degradation of receptor-bound human choriogonadotropin by lysosomotropic agents, protease inhibitors and metabolic inhibitors. J Biol Chem, 253, 7832-7838.

Ascoli, M. (1978). Demonstration of a direct effect of inhibitors of the degradation of receptor-bound human choriogonadotropin on the steroidogenic pathway. J Biol Chem, 253, 7839-7843.

Ascoli, M., Puett, D. (1978). Degradation of receptor-bound human choriogonadotropin by murine Leydig tumor cells. J Biol Chem, 253, 4892-4899.

Robinson, J. P., Derrebery, S., Liddle, R. A., Ascoli, M. & Puett, D. (1977). Renal and uptake of lutropin. Mol. Cell Biochem, 15, 63-66.

Ascoli, M., Ward, D. N. & Jirgensons, B. (1977). On the optical activity of ionized tyrosyl residues in ovine lutropin. Eur J Biochem, 72, 157-165.

Liu, W., Ascoli, M. & Ward, D. N. (1977). Ovine lutropin subunit isolation: comparison of salt precipitation and counter-current distribution procedures. J Biol Chem, 252, 5274-5279.

Ascoli, M., Liu, W. & Ward, D. N. (1977). Isolation and recombination of ovine lutropin subunit isolation with complete recovery of biological activity. J Biol Chem, 252, 5280-5286.

Holladay, L. A., Ascoli, M. & Puett, D. (1977). Conformational stability and self-association of zinc-free insulin at neutral pH. Biochem Biophys Acta, 494, 245-254.

Ascoli, M., Puett, D. (1977). Intracellular uptake and catabolism of lutropin by testicular tissue in vivo. FEBS Letters, 75, 77-82.

Ascoli, M., Puett, D. (1976). Biotransformations of pituitary luteinizing hormone in serum and urine. II. Evidence for reduced potency following urinary excretion. Endocrinology, 99, 1237-1243.

Ascoli, M., Puett, D. (1976). Biotransformations of pituitary luteinizing hormone in serum and urine. I. Association with serum components. Endocrinology, 99, 1229-1236.

Ascoli, M., Liddle, R. A. & Puett, D. (1975). The metabolism of luteinizing hormone: plasma clearance, tissue uptake and urinary excretion. Mol Cell Endocrinol, 3, 21-36.

Puett, D., Ascoli, M. & Holladay, L. A. (1975). Conformational and metabolic aspects of gonadotropins. Plenum Publishing Co., New York, 109-125.

Ascoli, M., Liddle, R. A. & Puett, D. (1975). Renal and hepatic lysosomal catabolism of luteinizing hormone. Mol Cell Endocrinol, 4, 297-310.

Ascoli, M., Puett, D. (1974). Tritium labeling of luteinizing hormone by reductive methylation. Biochem Biophys Acta, 37, 203-210.