Pharmacology

Mario Ascoli, PhD

Portrait

Mailing Address

Office: 2-530 BSB
Iowa City, IA 52242
Phone: +1 319 335 9907
Email: mario-ascoli@uiowa.edu

Office/Lab Address

Office/Lab: 2-505 BSB
Iowa City , 52242
Phone: +1 319 335 9907

Education

PhD, Biochemistry, Vanderbilt University, Nashville, TN, 1975

Appointments

Primary: Pharmacology
Secondary: Obstetrics & Gynecology

Center and Program Affiliations

  • Biosciences Graduate Program

Research Interests

G protein-coupled receptor, reproductive endocrinology, signaling network

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

  • The Leydig cell MEK/ERK pathway is critical for maintaining a functional population of adult Leydig cells and for fertility. Mol Endocrinol 25(7) : 1211-22, 2011. [PubMed]
  • 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) : 885-93, 2011. [PubMed]
  • 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) : 552-60, 2010. [PubMed]
  • Activation of the lutropin/choriogonadotropin receptor inhibits apoptosis of immature Leydig cells in primary culture. Endocrinology 150(8) : 3766-73, 2009. [PubMed]
  • The luteinizing hormone receptor-activated extracellularly regulated kinase-1/2 cascade stimulates epiregulin release from granulosa cells. Endocrinology 149(11) : 5549-56, 2008. [PubMed]
  • Arrestin-3 is essential for the activation of Fyn by the luteinizing hormone receptor (LHR) in MA-10 cells. Cell Signal 20(10) : 1822-9, 2008. [PubMed]
  • 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, 2008. [PubMed]
  • 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, 2008. [PubMed]
  • 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) : 3214-25, 2007. [PubMed]
  • Potential Leydig cell mitogenic signals generated by the wild-type and constitutively active mutants of the lutropin/choriogonadotropin receptor (LHR). Mol Cell Endocrinol 260-262 : 244-8, 2007. [PubMed]