| Faculty Member ProfileJohn A. McCracken Ph.D., B.V.M.S., M.R.C.V.S. Professor-in-Residence |
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| Faculty Member ProfileJohn A. McCracken Ph.D., B.V.M.S., M.R.C.V.S. Professor-in-Residence |
| Background | ~ | Research Interests | ~ | Recent Publications | ~ | Hobbies or Non-Academic Interests | ~ | Favorite Links |
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Dr. McCracken was born in Cathcart a suburb of Glasgow, Scotland, but grew up in Troon in the county of Ayrshire, noted for its golf courses such as Royal Troon and Turnberry, not to mention its Ayrshire cattle and Clydesdale horses. He was interested in a career in either Agriculture or Medicine, but as a compromise he chose to enroll in Veterinary Medicine at Glasgow University. After graduating in 1958, he served as a House Surgeon at the Veterinary Hospital in Bearsden, Glasgow. This invaluable experience enabled him to develop skills in surgery and clinical medicine as well as to gain insights into ongoing research. At the end of that year, Sir William Weipers, Dean of the School, convinced John to pursue a Research Fellowship supported by the Scottish Milk Marketing Board. With considerable trepidation, John accepted this directional change in his career. Weipers must have seen in John some hidden talent of which he was completely unaware! John elected to spend the first year of the Fellowship at the University of Cambridge,UK with Roger Short to learn the intricacies of steroid hormone measurement. On returning to Glasgow, John completed his Ph.D. dissertation which included the discovery of progesterone in cow’s milk, later developed into a simple bovine early pregnancy test that is still widely used today. For post-doctoral work, his first choice was the Worcester Foundation for Experimental Biology, in Shrewsbury, Massachusetts, then “Mecca” for the steroid biochemist. When Weipers told John that the post-doctoral fellowship was confined to the UK, John secured a position with the leading light in the steroid field in the UK, Professor Ian Bush at the University of Birmingham Medical School, UK. After two years (1963 & 1964), Bush called John into his office to say that he was immigrating to the United States to a place called the Worcester Foundation for Experimental Biology and would John like to join Bush and his group there! Needless to say, John tactfully accepted Bush’s offer but neglected to mention that the Worcester Foundation had been his original first choice! My exodus with Bush and colleagues to the US gave birth to the term “Brain Drain” and indirectly improved funding for science in the U.K. It was not until many years later that John told Professor Bush that his lab had actually been his second choice for post doctoral studies and they both had a good laugh! Little did Dr. McCracken know that, with a year off in 1970 as a Visiting Professor at Cornell University with Professor William Hansel, he was to spend the next 34 years at the Worcester Foundation.
Research Accomplishments/Interests:
After arriving at the Worcester Foundation, Gregory Pincus, the co-founder of the Institute and of birth control pill fame, guided John into the study of the inter-relationships of steroid hormones and prostaglandins. This study culminated 1972, in collaboration with Bengt Samuelsson in Sweden, with the identification of prostaglandin-F2a as the long sought luteolytic hormone that controls the ovarian cycle in most mammals. This work was published in Nature with the capsular subheading: Prostaglandin F2a is released from the uterus of the sheep in a cyclic fashion, acts primarily in a local manner on the ovary via a counter-current mechanism, and is responsible for the periodic regression of the corpus luteum in this species. Such a discovery proved to be a major breakthrough in the livestock industry where PGF2a or its synthetic analogs are now used routinely to regulate the breeding of domestic animals. Further work revealed that estrogen and progesterone controlled the release of the uterine luteolytic hormone, PGF2a, via the induction of receptors for oxytocin in the endometrium. At the end of the cycle, intermittent releases of oxytocin from the posterior pituitary, as well as from the corpus luteum itself, interacting with the newly formed endometrial receptors for oxytocin, invoke the pulsatile release of PGF2a from the uterus. Moreover, it was found that a finite number of uterine pulses of PGF2a, usually five, was required to cause complete regression of the corpus luteum and hence the induction of a new ovarian cycle. It was also determined that, in the event of pregnancy, the induction of endometrial receptors for oxytocin failed to occur, thus preventing the pulsatile release of PGF2a from the uterus, and thereby allowing the corpus luteum to survive and maintain the pregnancy. Later work by others showed that the blockade of endometrial oxytocin receptors in early pregnancy is due to the secretion of interferon-tau by the developing blastocyst. Other work with prostaglandins included the discovery, with Robert Skarnes an immunologist also at the Worcester Foundation, that fever induced by bacterial endotoxin is caused by the generation in the systemic circulation of prostaglandin-E2 which diffuses into the thermoregulatory center in the brain and evokes the first wave of fever. Recent work by others has shown that the second more sustained wave of fever is also caused by prostaglandin-E2, but this time induced locally within the thermoregulatory center in the brain. These findings now explain why both waves of fever are prevented by prostaglandin blocking drugs such as aspirin and acetominaphen (Tylenol).
In 1998, Dr. McCracken retired from the Worcester Foundation as Principal Scientist Emeritus at the time that the Institute was being disbanded. He was then appointed as Professor-in-Residence in the Department of Animal Science at the University of Connecticut where his research has focused on molecular aspects of prostaglandin action, in particular on the mechanism of action of PGF2a in causing regression of the corpus luteum. This research has involved collaboration with Dr. Paul Tsang in the Department of Animal Science at UNH, as well as several members of the Department of Animal Science at UConn. Current work has shown that one of the earliest changes so far reported in the luteolytic action of PGF2a in vivo, is the dramatic change in protein regulators of the extracellular matrix of the corpus luteum. The overall objective of the study is to obtain a detailed picture of the dynamic in vivo temporal changes in a variety of other proteins in the corpus luteum throughout the luteolytic process. Such studies on the growth and regression of the corpus luteum are clearly indicated, not only for understanding basic reproductive processes, but also because the mechanisms controlling the function of this transient gland have important implications for understanding the basis for controlled and uncontrolled growth and regression of other tissues. . In other studies, Dr. McCracken has formed a collaboration with Dr. Joe Arosh and Dr. Sakhila Banu at Texas A&M University to study the role of the prostaglandin transporter protein in the countercurrent transfer of PGF2a within the ovarian pedicle which permits PGF2a to reach the ovary directly thus avoiding catabolism in the pulmonary circulation. In a recent study, Dr. McCracken has collaborated with a group in Sweden headed by Professor Mats Brännström who’s long term goal is to transplant the human uterus in order to ameliorate certain types of infertilty in women. This collaboration both here at UConn and in Sweden has resulted in a uterine transplantation procedure in sheep which will serve as an excellent model for future uterine transplantation in women. Over the years, Dr. McCracken’s work has been supported by competitive grants from NSF, NIH, and most recently by two competitive grants from the USDA and a competitive Internal Research Award from the UConn Foundation.
If anyone would like to learn more about the luteolytic hormone or prostaglandins and leukotrienes in general, John will be glad to send copies of recent textbook chapters on these topics to them. John can be reached at: john.mccracken@uconn.edu
1958-1959 House Surgeon, Veterinary Hospital, University of Glasgow (Clinical Medicine and Surgery).
1959-1960 Visiting Research Fellow, University of Cambridge (Dr. R.V. Short, Biochem & Physiol)
1960-1963 Research Fellow, University of Glasgow (Progesterone Metabolism - Professor Sir William Weipers)
1963&1964 Research Fellow, University of Birmingham, (Prof. Ian E. Bush - Steroid Biochemistry)
1964-1970 Staff Scientist, Worcester Foundation (Steroid Biochemistry, Endocrinology)
1969-1970 Visiting Professor, Cornell University, (Prof. William Hansel - taught course in Steroid Biochem).
1970-1992 Senior Scientist Worcester Foundation
1976-1986 Affiliate Scientist, New England Regional Primate Res Center, Southboro, MA
1977-1998 Research Professor of Physiology, U.Mass. Medical School, Worcester, MA
1992-1997 Principal Scientist, Worcester Foundation
1998 Principal Scientist Emeritus, Worcester Foundation
1998-Present Professor-in-Residence, University of Connecticut, Storrs, CT
Honors/Activities:
Member, Biochemical Endocrinology Study Section, NIH, 1979-1983
Opponent in Ph.D. Thesis Defense, University of Gothenburg, Sweden for Candidate Arnie
Bendz, M.D., "Evidence for a counter-current system in the human adnexa", March 1982
Member, Publications Committee, Society for the Study of Reproduction, 1983-1984
Member, Reproductive Endocrinology Study Section, NIH, 1984-1988
Member, Review Committee, McMaster Reproductive Biology Program, February 1985
Member, Steering Committee, Worcester Consortium Ph.D. Program, 1986-1996
Opponent in Ph.D. Thesis Defense, University of Uppsala, Sweden for Ph.D. candidate Dr.
Samar Basu, "Endometrial prostaglandin synthesis", September 1988
Organizer NIH Conference on Autocrine and Paracrine Mechanisms in Reproductive
Endocrinology, Worcester Foundation, October 14-16, 1988.
Editor, Book entitled, Autocrine and Paracrine Mechanisms in Reproductive Endocrinology, 1989
Chairman, Gregory Pincus Memorial Lecture Committee, 1980-1998 (organized lecture and
associated symposia)
Chairman and Organizer, New England Endocrinology Conference, 1975, 1980, 1990
Member, Awards Committee, Society for the Study of Reproduction, 2001-2003
Memorial Lecture for Jack Carlson, SORB Conference, London Ontario, Canada , April, 2005
Opponent in Ph.D.Thesis Defense, University of Gothenberg, Sweden for Ph.D. Candidate
Pernilla Dahm-Kahler, MD. “The Ovulatory Process: Studies in the Human and the Rabbit”.
March, 2006.
American Association for the Advancement of Science
Federation of American Scientists
Endocrine Society
Society for the Study of Reproduction
Society for the Study of Fertility
New York Academy of Sciences
Massachusetts Society for Medical Research
Ferguson, D.E., Tsang, P.C.W., Schreiber, D.T., Keator, C.S., and McCracken, J.A. 2007. In vivo changes in protein expression of gelatinases and tissue inhibitors of metalloproteinases (TIMP-1) in the ovine corpus luteum after multiple pulses of prostaglandin F2a. Abstract, 40th Annual Meeting of the Society for the Study of Reproduction, San Antonio, TX.
McCracken, J.A., Custer, E.E., Schreiber, D.T., Hoagland,T. and Keator, C.S. 2007. Luteal oxytocin secretion and ovarian blood flow is stimulated by neurpeptide Y in sheep. Abstract, 40th Annual Meeting of the Society for the Study of Reproduction, San Antonio, TX.
Dahm-Kähler, P., Lundmark,C., Enskog, A., Almen-Wranning, C., Racho El-Akouri, R., McCracken, J.A. and Brännström, M. (2007). Orthoptic autotransplantation of the uterus in the sheep: methodology and early reperfusion events. In press: J. Obstet. Gynec. Res.
Keator, C.S., Schreiber, D.T., Hoagland, T.A., McCracken,J.A., and Milvae,R.A. (2007).Intrauterine infusion of BQ-610, an endothelin type A receptor antagonist, delays luteolysis in dairy heifers. In press: Dom. Anim. Endo
Keator, C.S., Schreiber, D.T., Hoagland, T.A., and McCracken,J.A. (2007) Luteolytic and luteotropic effects of nitric oxide in vivo are dose dependent in sheep. Under revision for Domestic Animal Endocrinology.
Keator, C.S., Hoagland, T.A., Schreiber, D.T., Tsang, P.C.W., Ferguson, D.E., and McCracken,JA (2007) Submitted to Reproduction 04-05-07. Nitric oxide regulates ovarian function in a dose-dependent manner in sheep.
Dahm-Kähler, P., Lundmark,C., Enskog, A., Almen-Wranning, C., Racho
El-Akouri, R., McCracken, JA and Brännström, M. (2007). Submitted to Human Reproduction 03-04-07. Orthoptic autotransplantation of the uterus in the sheep: methodology and early reperfusion events.
McCracken JA, Glew ME, Scaramuzzi R, (1970). J Clin Endo Metab 30:544-546. Corpus luteum regression induced by prostaglandin F2a. McCracken JA, (1971). Ann NY Acad Sci 180:456-472. Prostaglandin F2a and corpus luteum regression. McCracken JA, Baird DT, Goding JR, (1971). Recent Progress Hormone Res 27:537-582. Factors affecting the secretion of steroids from the transplanted ovary of the sheep. McCracken JA, Carlson JC, Glew ME, Goding JR, Baird DT, Green K, Samuelsson B, (1972). Nature New Biol (London) 238:129-134. Prostaglandin F2a identified as a luteolytic hormone in sheep. McCracken JA, Barcikowski B, Carlson JC, Green K, Samuelsson B, (1973). Advances in Biosciences 9:599-624. The physiological role of prostaglandin F2a in regression of the corpus luteum. Barcikowski B, Carlson JC, Wilson L, McCracken JA, (1974). Endocrinology 95:1340-1349. The effect of endogenous and exogenous estradiol-17B on the release of PGF2a from the ovine uterus. Roberts JS, Barcikowski B, Wilson L, Skarnes RC, McCracken JA, (1975). J Steroid Biochem 6:1091-1097. Hormonal and related factors affecting the release of PGF2a from the uterus. Skarnes, R.C., and J.A. McCracken (1980). Microbiology-1980, 162-165, March. The mediating role of prostaglandin E in endotoxin fever. Skarnes, R.C., S.K. Brown, S.S. Hull, Jr., and J.A. McCracken (1981). J. Experimental Med. 154: 1212-1224. The role of prostaglandin E in the biphasic fever response to endotoxin. McCracken JA, (1980). In: Advances in Prostaglandin and Thromboxane Research 8:1329-1344. Eds: Ramwell P, Samuelsson B, and Paoletti R. Pub: Raven Press, New York. Hormone receptor control of prostaglandin secretion by the ovine uterus. Schram W, Bovaird LC, Glew ME, Schramm G, McCracken JA, (1983). Prostaglandins 26:347-364. Corpus luteum regression induced by ultra-low pulses of PGF2a. McCracken JA, Schramm W, Okulicz WC, (1984). Animal Reprod Sci 7:31-55. Hormone receptor control of pulsatile secretion of PGF2a from the ovine uterus during luteolysis and its abrogation during early pregnancy. Leavitt WW, Okulicz WC, Schramm W, Robidoux WF, McCracken JA, (1985). J Steroid Biochem 22:687-691. Estrogen receptor and oxytocin receptor evolution in the ovine uterus following progesterone withdrawal. McCracken JA, Schramm W, (1988). In: Prostaglandins: Biol and Chem of Prostaglandins and Related Eicosanoids. Ed: PB Curtis-Prior. Pub: Churchill-Livingstone, Edinburgh. Chap 34, pp425-462. Prostaglandins and corpus luteum regression. Lamsa JC, Kot SJ, Eldering JA, Nay MG, McCracken JA, (1989). Biol Reprod 40:1215-1223. Prostaglandin F2a-stimulated release of ovarian oxytocin in the sheep in vivo: threshold and dose dependency. Ivell R, Hunt N, Abend N, Brackman B, Nollmeyer D, Lamsa JC, McCracken JA, (1990). Reprod Fert Dev 2:703-711. Structure and ovarian expression of the oxytocin gene in the sheep. Lamsa JC, Cushman RA, Nay MG, McCracken JA (1992). Prostaglandins 43:165-179. In vivo desensitization of a high affinity PGF2a receptor in the ovine corpus luteum. Custer EE, Lamsa JC, Eldering JA, McCracken JA, (1995). Endocrine 3:761-764. Identification of functional high and low affinity states of the prostaglandin F2a receptor in the ovine corpus luteum in vivo and their role in hormone pulsatility. McCracken JA, Custer EE, Lamsa JC, Robinson AG, (1995). Adv Exp Med Biol 395:133-154. The central oxytocin pulse generator: a pacemaker for luteolysis. Custer EE, Eldering JA, Lamsa JC, McCracken JA, (1996). Reprod Dom Anim 31:449-454. Differential actions of PGF2a on the ovine corpus luteum. McCracken JA, Custer EE, Lamsa JC, (1999) Physiological Reviews 79:263-323. Luteolysis: a neuroendocrine-mediated event. Towle T, Tsang PCW, Milvae RA, Newbury MK, McCracken JA, (2002). Biol Reprod 66:1515-1521. Dynamic in vivo changes in tissue inhibitors of metalloproteinases-1 and -2, and matrix metalloproteinases -2 and -9, during prostaglandin F2a-induced luteolysis in sheep. McCracken JA. (2004). Prostaglandin F2a: The Luteolytic Hormone. In: The Eicosanoids. Ed: P Curtis-Prior. Pub: John Wiley & Sons, London & New York. Chapter 50, pp525-545. McCracken JA. (2005). Prostaglandins and Leukotrienes. In: Endocrinology: Basic and Clinical Principles. 2nd Edition, Eds. P. Michael Conn & Shlomo Melmed. Pub: Humana Press, Totowa, NJ. Chapter 7, pp93-111. .Dahm-Kähler, P., Lundmark,C., Enskog, A., Almen-Wranning, C., Racho
John’s hobbies include tennis, flyfishing and the collection of rare single malts. He tries to visit Scotland every other year and has a penchant for staying in castles, which have included Brodick, Barcaldine, and Fyvie, famous for its Bonnie Lass! He also has a long standing interest in conservation and is a life member of the Sierra Club, Massachusetts Audubon Society, Trout Unlimited, and the National Trust for Scotland. http://anscigallery.nal.usda.gov//index.php http://www.tu.org/site/pp.asp?c=7dJEKTNuFmG&b=275410 Hobbies or Non-Academic Interests: