Research Interests

My laboratory continues to focus on the non-genomic actions of steroid hormones in human sperm and platelets. The studies in sperm currently focus on the defining the mechanism by which progesterone stimulates calcium influx in human and monkey sperm. We have recently shown that progesterone does not promote calcium influx through T-type calcium channels, whereas the neoglycoprotein mannose coupled to albumin does promote calcium influx through T-type calcium channels. This ligand possibly weakly simulates the natural ZP3 ligand which sperm bind to during fertilization. The studies in the monkey sperm show that cAMP greatly potentiates the ability of progesterone to promote calcium influx.

The studies in platelets have shown that several progesterone metabolites (e.g. pregnanolone and pregnanediol) are platelet activators. Levels of several progesterone metabolites are elevated during the third trimester of pregnancy and this may be one of the reasons why there is increased thrombosis during the third trimester and also postpartum. Venous thromboembolic disease is the commonest cause of maternal death. These metabolites stimulate calcium influx in platelets and promote platelet aggregation. The metabolites appear to interact with a cell surface receptor that is coupled to phospholipase C, possibly through a G-protein.

In collaboration with Dr. Roy Williams (Old Dominion University) and Yuliya Dobrydneva (Graduate student), we have been investigating the mechanism by which the phytoestrogenic compound trans-resveratrol (TR), which is found in appreciable quantities in grape skins and wine, is able to inhibit platelet aggregation both in vivo and in vitro. We have shown that TR inhibits Ca influx into thrombin-stimulated platelets. Since TR is rather polar and the effect is rapid, this indicates that TR interacts with a target on the cell surface, without having to enter the platelet. TR also inhibits spontaneous Ba (calcium surrogate) entry into platelets, which indicates that TR directly affects Ca channel activity. TR also inhibits thapsigargin-mediated Ca influx into platelets, suggesting that the Store-Operated Calcium Channel (SOCC) is one of the possible targets of TR. The effects of several estrogens and phytoestrogens on detrusor muscle contractions are also being studied in collaboration with Dr. Paul Ratz.

Recent Publications

Augert, G., Blackmore, P.F. and Exton, J.H. Changes in the concentration and fatty acid composition of phosphoinositides induced by hormones in hepatocytes. J. Biol. Chem. 264:2574-2580, 1989

Blackmore, P.F. and Exton, J.H. Ca2+ fluxes and phosphoinositides in hepatocytes. Methods Enzymology 173:534-545, 1989

Lynch, C.J., Blackmore, P.F., Johnson, E.H., Wange, R.L., Krone, P.K. and Exton, J.H. Guanine nucleotide binding regulatory proteins and adenylate cyclase in livers of streptozotocin- and BB/Wor-diabetic rats J. Clin. Invest. 83:2050-2062, 1989

Blackmore, P.F. and Augert, G. Effect of hormones on cytosolic free calcium in adipocytes. Cell Calcium 10:561-567, 1989

Augert, G., Bocckino, S.B., Blackmore, P.F. and Exton, J.H. Hormonal stimulation of diacylglycerol formation in hepatocytes. Evidence for phosphatidylcholine breakdown. J. Biol. Chem. 264:21689-21698, 1989

Cited over 200 times

Blackmore, P.F., Beebe, S.J., Danforth, D.R. and Alexander, N. Progesterone and 17 alpha-hydroxyprogesterone. Novel stimulators of calcium influx in human sperm. J. Biol. Chem. 265:1376-1380, 1990

Kelley, L.L., Blackmore, P.F., Graber, S.E. and Stewart, S.J. Agents which raise cAMP in human T lymphocytes release an intracellular pool of calcium in the absence of inositol phosphate production. J. Biol. Chem. 265:17657-17664, 1990

Ratz, P.H. and Blackmore, P.F. Differential activation of rabbit femoral arteries by aluminum fluoride and sodium fluoride. J. Pharmacol. Exp. Ther. 254:514-520, 1990

Mahony, M.C., Fulgham, D., Blackmore, P.F. and Alexander, N.J. Elevation of human sperm-zona pellucida tight binding by presence of monoclonal antibodies to sperm antigens. J. Reprod. Immunol. 19:269-285, 1991

Mahony, M.C., Blackmore, P.F., Bronson, R.A. and Alexander, N.J. Inhibition of human zona pellucida tight binding in the presence of antisperm antibody positive polyclonal patient sera. J. Reprod. Immunol. 19:287-301, 1991

Blackmore, P.F., Neulen, J., Lattanzio, F.A. and Beebe, S.J. Cell surface receptors for progesterone mediate calcium uptake in human sperm. J. Biol. Chem. 266:18655-18659, 1991

Blackmore, P.F., Mojsov, S., Exton, J.H. and Habener, J.F. Absence of insulinotropic glucagon-like peptide - (7-37) receptors on isolated rat liver hepatocytes. FEBS Lett. 283:7-10, 1991

Blackmore, P.F. and Lattanzio, F.A. Localization of progesterone receptors on the head of human sperm. Biochem. Biophys. Res. Commun. 181:331-336, 1991

Oehninger, S. Clark, G.F., Fulgham, D., Blackmore, P.F., Mahony, M.C., Acosta, A.A. and Hodgen, G.D. Specificity of the antagonistic effect of fucoidin on human sperm-zona pellucida interactions. J. of Andrology 13:519-525, 1992

Brucker, C., Sandow, B.A., Blackmore, P.F., Lipford, G.B. and Hodgen, G.D. Monoclonal antibody AG7 inhibits fertilization post sperm-zona binding. Molecular Reprod. Development 33:451-462, 1992

Blackmore, P.F., Oakes, S.G. and Somers, K.D. Influence of K-ras transformation on H1-histamine signaling in Balb/3T3 cells. Oncogene 7:2053-2057, 1992

Blackmore, P.F. Role of p21ras in hormone signaling and cell growth. Adv. Exp. Med. Biol. 321:143-146, 1992

Blackmore, P.F. Thapsigargin elevates and potentiates the ability of progesterone to increase intracellular free calcium in human sperm. Cell Calcium 14:53-60, 1993

Bocckino, S.B. and Blackmore, P.F. Hepatic inositol phosphate and lipid messenger systems. In: Hepatic Transport and Bile Secretion: Physiology and Pathophysiology (N. Taroloni and P.D. Berk, eds.) Raven Press Ltd. New York pp. 531-537, 1993

Blackmore, P.F., McPherson, R.K. and Stevenson, R.W. Actions of a novel antidiabetic agent englitazone (CP 68,722) in rat hepatocytes. Metabolism 42:1583-1587, 1993

Neulen, J., Ishikawa, K., Blackmore, P.F. and Beebe, S.J. Identification and characterization of a novel progesterone binding protein in human semen. Endocrine J. 1:397-404, 1993

Blackmore, P.F. Rapid nongenomic actions of progesterone stimulate Ca2+ influx and the acrosome reaction in human sperm. Cellular Signalling 5:531-538, 1993

Oehninger, S., Blackmore, P., Morshedi, M., Sueldo, C., Acosta, A.A. and Alexander, N.J. Defective calcium influx and acrosome reaction (spontaneous and progesterone-induced) in spermatozoa of infertile men with severe tetratozoospermia Fertil. Steril. 61: 349-354, 1994

Kamada, S., Blackmore, P.F., Oehninger, S., Gordon, K. and Hodgen, G.D. Existence of P2-purinoceptors on human and porcine granulosa cells. J. Clin. Endocrinol. and Metabolism 78:650-656, 1994

Kamada, S., Oehninger, S., Mahony, M.C., Blackmore, P.F., Lanzendorf, S.E. and Hodgen, G.D. Does endothelin - 1 affect human spermatozoa function? Am. J. Reprod Immunol. 31:91-98, 1994

Blackmore, P.F., Im, W.B. and Bleasdale, J.M. The cell surface progesterone receptor on human sperm is unlike the A ring reduced steroid site on the GABAA receptor/chloride channel. Mol. Cell Endocrinol. 104:237-243, 1994

Kamada, S., Blackmore, P.F., Kubota,T., Oehninger, S., Asada, Y., Gordon, K., Hodgen, G.D., and Aso,T. The role of endothelin-1 in regulating human granulosa cell proliferation and steroidogenesis in vitro. J. Clin. Endocrinol. and Metabolism 80: 3708-3714, 1995

Morshedi, M., Oehninger, S., Blackmore, P.F., Bocca, S., Coddington, C. and Hodgen, G.D. Investigation of some biochemical and functional effects of cryopreservation of human spermatozoa using an automated freezing-quick-thawing method. Int.J. of Andrology 18: 279-286,1995

Rosenthal, M.D., Rzigalinski, B.A., Blackmore, P.F. and Franson, R.C. Cellular regulation of arachidonate mobilization and metabolism. Prostaglandins Leukotrienes and Fatty Acids 52: 93-98, 1995

Oehninger, S., Blackmore, P.F., Mahony, M., and Hodgen, G. Effects of hydrogen peroxide on human spermatozoa. J. Assisted Reprod. and Genetics. 12:40-46,1995

Blackmore, P.F., Fisher, J.F., Spilman, C.H., Im, W.B. and Bleasdale, J.H. Effects of Steroids on Calcium Fluxes in Human Sperm. in Human Acrosome Reaction. (eds P.Fenichel, J. Parinaud) Colloque INSERM/ John Libbey Eurotext Ltd. 236:165-177,1995

Alexander, N.J., Kim, H.K., Blye, R.P. and Blackmore, P.F. Steroid Specificity of the Human Sperm Progesterone Receptor. Steroids. 61:116-125,1996

Rzigalinski, B.A., Blackmore, P.F. and Rosenthal, M.D. Arachidonate mobilization is coupled to depletion of intracellular calcium stores and influx of extracellular calcium in differentiated U937 cells. Biochim. Biophys. Acta. 1299: 342-352, 1996

Blackmore, P.F., Fisher, J.F., Spilman, C.H. and Bleasdale, J.M. Unusual steroid specificity of the novel cell surface progesterone receptor on human sperm. Mol. Pharm. 49: 727-739, 1996

Wasilenko, W.J., Kohn,E.C., Palad, A.J., Somers, K.D., Blackmore, P.F., Rhim, J.S., Wright, G.L. and Schellhamer, P.F. Effects of the calcium influx inhibitor carboxyamido-triazole on the proliferation and invasiveness of human prostate tumor cell lines. Intl. J. Cancer. 68: 259-264, 1996

Wasilenko, W.J., Cooper, J., Palad, A.J., Somers, K.D., Blackmore, P.F., Wright, G.L. and Schellhammer, P.F. Calcium signaling in prostate cancer cells: evidence for multiple receptors and enhanced sensitivity to bombesin/GRP. Prostate. 30: 167-173, 1997

Wu, Yangguan, Palad, A.J., Wasilenko, W.J., Blackmore, P.F., Pincus, W.A., Schechter, G.L., Spoonster, J.R., Kohn, E.C. and Somers, K.D. Inhibition of head and neck squamous cell carcinoma growth and invasion by the calcium influx inhibitor, carboxyamido-triazole. Clinical Cancer Research. 3:1915-1921, 1997

Nassar, A., Mahoney, M., Blackmore, P.F., Morshedi, M., Ozgur, K., and Oehninger, S. Alteration of intracellular calcium is not a causal mechanism for pentoxifylline-induced hyperactivated motility or acrosome reaction. Fertil. Steril. 69: 748-754, 1998

Glazier, A.T., Blackmore, P.F., Nolan, R.D., and Wasilenko, W.J. Attenuation of LPA-mediated calcium signaling and inositol polyphosphate production in rat-1 fibroblasts transformed by the v-src oncogene. Biochem. Biophys. Res. Commun. 245: 607-612,1998

Gresham, J., Margiotta, P., Palad, A., Somers, K., Blackmore, P.F., Wright, G.L., Schellhammer, P., and Wasilenko, W. Involvement of Shc in the signaling response of human prostate tumor cell lines to epidermal growth factor. Int. J. Cancer. 77: 923-927, 1998.

Blackmore, P.F. News and views of non-genomic progesterone receptors on spermatozoa. Andrologia 30: 255-261, 1998.

Blackmore, P.F. Extragenomic actions of progesterone in human sperm and progesterone metabolites in human platelets. Steroids 64: 149-156, 1999.

Dobrydneva, Y., Williams, R.L., and Blackmore, P.F. trans-Resveratrol inhibits calcium influx in thrombin-stimulated human platelets. Br. J. Pharmacol. 128: 149-157, 1999.

Blackmore, P.F. and Eisoldt S. The neoglycoprotein mannose-albumin, but not progesterone, activates T-type calcium channels in human sperm. Mol. Human Reprod. 5: 101-109, 1999.

Shenfeld, O.Z., McCammon, K.A., Blackmore, P.F., and Ratz, P.H. Rapid effects of estrogen and progesterone on tone and spontaneous rhythmic contractions of the rabbit bladder. Urology Res. 27: 386-392, 1999

Ratz, P.H., McCammon, K.A., Altstatt, D., Blackmore, P.F., Shenfeld, O.Z., and Schlossberg, S.M. Rapid inhibition of bethanocol- and alpha,beta-methylene ATP- induced detrusor contractions by estradiol, progesterone and genistein. J. Urol. 162: 1821-1828, 1999