Ov D. Slayden
Disorders
of the reproductive tract including tubal infertility, endometriosis and
excessive uterine bleeding continue to levy a heavy burden on women's health.
In order to identify new therapies for the treatment and prevention of these disorders
we must advance our fundamental knowledge regarding basic physiology of the
reproductive tract.
The
Slayden laboratory investigates factors that mediate the action of estrogens
and progestins in the macaque reproductive tract. Techniques including
immunocytochemistry, ligand binding, western blotting, RealTime RT-PCR and in
situ hybridization are applied to understand the cyclic effects of ovarian
hormones on the uterus, oviduct and cervix. Recent studies in Dr. Slayden’s
laboratory have focused extensively on the application of progesterone
antagonists (antiprogestins) to regulate cellular function in the tract.
Antiprogestins block progesterone action and can also specifically inhibit
estrogen-stimulated uterine cell proliferation. Slayden and colleagues have
shown that antiprogestins strikingly increase androgen receptor in the
endometrium and that local androgens may play an important role in the
antiproliferative effects of these important therapeutic compounds. In
collaborative studies with Dr. Robert M. Brenner and Dr. Hilary Critchley at
the Centre for Reproductive Biology at the University of Edinburgh, Dr.
Slayden's group is also studying the use of antiprogestins to control uterine
bleeding in women who use progestin releasing intrauterine devices.
Another area of interest for the Slayden lab is endometriosis, a disease in
which endometrium-like lesions exist at sites outside the uterus. Like women,
rhesus macaques develop endometriosis, and Dr. Slayden's laboratory is
investigating the effects of estrogen and estrogen antagonists on ectopic
endometrium in rhesus macaques. In recent studies conducted in collaboration
with Dr. Laura Greenberg, M.D., and Jeffrey Jensen M.D. , Slayden and colleagues have demonstrated that
both macaque and human endometriosis can be engrafted into immunodeficient mice
to provide a unique model for the evaluation of anti-endometriotic therapies on
the human disease.
BIOGRAPHY
Ov Daniel Slayden is an assistant scientist in the Division
of Reproductive Sciences at ONPRC and has a joint appointment in the Department
of Obstetrics and Gynecology in the School of Medicine, OHSU. He received his
B.A. and M.A. degrees in Biology from Sonoma State University, and earned a
Ph.D. in Biochemistry and Animal Science at Oregon State University. Dr.
Slayden moved to the Center in 1991 after being awarded a Reproductive Biology
Training Fellowship through the Department of Physiology at OHSU.
KEY PUBLICATIONS
Slayden,
O.D., K. Chwalisz, R.M. Brenner. (2001) Reversible suppression of menstruation
with progesterone antagonists in rhesus macaques. Hum. Repro. 16:1562-1574. PMID
11473944
Slayden,O.D., N.R. Nayak, K.A. Burton, K. Chwalisz, S.T. Cameron, H.O.
Critchley, D.T. Baird, R.M. Brenner. (2001) Progesterone antagonists increase
androgen receptor expression in the rhesus macaque and human endometrium. J.
Clin. Endocrinol.Metab. 86:2668-2679. PMID 11397870
Slayden,O.D., R.M. Brenner. (2003) Flutamide counteracts the antiproliferative
effects of antiprogestins in the primate endometrium. J. Clin. Endocrinol.
Metab. 88:946-949. PMID 12574238
Greenberg, L.H., O.D. Slayden. (2004) Human endometriotic xenografts in
immunodeficient RAG-2/gamma(c)KO mice. Am. J. Obstet. Gynecol. 190:1788-1795. PMID
15284801
Brenner,R.M., O.D. Slayden. (2004) Steroid receptors in blood vessels of the
rhesus macaque endometrium: a review. Arch. Histol.Cytol. 67:411-416. PMID 15781982
Slayden,O.D., R.M. Brenner. (2004) Hormonal regulation and localization of
estrogen, progestin and androgen receptors in the endometrium of nonhuman
primates: effects of progesterone receptor antagonists. Arch. Histol. Cytol.
67:393-409. PMID 15781981
Carroll RL, Mah K, Fanton
JW, Maginnis GN, Brenner RM, Slayden OD. Assessment of menstruation in the
vervet (Cercopithecus aethiops). Am J
Primatol. 2007 Aug;69(8):901-16.
Nayak NR,
Slayden OD, Mah K, Chwalisz K,
Slayden OD,
Keator CS. Role of progesterone in
nonhuman primate implantation. Semin
Reprod Med. 2007 Nov;25(6):418-30. PMID 17960526
Zhang Z,
Lundeen SG, Slayden O, Zhu Y, Cohen J, Berrodin TJ, Bretz J, Chippari S, Wrobel
J, Zhang P, Fensome A, Winneker RC, Yudt MR.
In vitro and in vivo characterization of a novel nonsteroidal,
species-specific progesterone receptor modulator, PRA-910. Ernst Schering Found Symp Proceedings,
1:171-197, 2007. PMID 18540573
Cao W, Mah
K, Carroll RS, Slayden OD, Brenner RM.
Progesterone withdrawal up-regulates fibronectin and integrins during
menstruation and repair in the rhesus macaque endometrium. Hum Reprod 22:3223-3231, 2007. PMID 17962213
Fensome A,
Adams WR, Adams AL, Berrodin TJ, Cohen J, Huselton C, Illenberger A, Kern JC,
Hudak VA, Marella MA, Melenski EG, McComas CC, Mugford CA, Slayden OD, Yudt M,
Zhang Z, Zhang P, Zhu Y, Winneker RC, Wrobel JE. Design, synthesis, and SAR of new
pyrrole-oxindole progesterone receptor modulators leading to 5-(7-fluoro-3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile
(WAY-255348). J Med Chem, 51:1861-1873,
2008. PMID 18318463
Bishop CV,
Filtz T, Zhang Y, Slayden OD, Stormshak, F.
Progesterone suppresses an oxytocin-stimulated signal pathway in COS-7
cells transfected with the oxytocin receptor.
Steroids, 73:1367-1374, 2008.
PMID 18674552
To see a full listing of Dr. Slayden's publications click here
