Office: SG Mudd 278
Office Phone: (303) 871-3454
Lab Phone: (303) 871-3459
1977 B.A., Chemistry - The Colorado College - Colorado Springs, CO
1982 Ph.D., Pharmacology - University of Colorado School of Medicine - Denver, CO
Steroid hormones (progestins and androgens) and peptide hormones (insulin and insulin-like growth factor 1) stimulate meiotic division in amphibian oocytes - stimulating the development of oocyte to egg. Amphibian oocytes are large and distinctly pigmented cells that can be microinjected under a stereomicroscope. Biochemical events can then be correlated with and compared to the meiotic maturation response that is indicated by white spot formation as the nucleus moves to the surface of the cell and pushes aside the melanin pigment before spindle formation and polar body extrusion.
Over the years, my lab team has studied the early molecular events that trigger meiotic cell division. We have collected evidence showing that hormone-induced triggering mechanisms include:
inhibition of adenylyl cyclase (the enzyme that synthesizes cAMP) independent of the G-alpha-i subunit of heterotrimeric G protein (by progesterone and IGF-1)
stimulation of cGMP-inhibited phosphodiesterase type 3 (by insulin, IGF-1 and ras protein)
migration of p21ras protein to the oocyte membrane (by insulin)
receptor-mediated endocytosis of the insulin/IGF-1 receptor (by insulin and IGF-1)
inhibition of farnesyl transferase activity (by insulin and IGF-1) [this is the enzyme that attaches lipid anchors to the p21ras protein]
Currently, the lab is evaluating how oocyte membrane fluidity and cholesterol-rich, low-density membrane domains might be affected by inducing hormones.
View Sadler's publications through PubMed