Gadsby, John E., PhD
Associate Professor of Physiology,
Dept. of Anatomy, Physiological Sciences and Radiology,
College of Veterinary Medicine, North Carolina State University

Ph.D.: University of Cambridge, U.K., 1979.
Reproductive Physiology/Endocrinology.
(Dr. Brian Heap - Advisor)
Postdoctoral Training: University of Michigan 1979-1985
Reproductive Endocrinology/Reproductive Sciences Program.
Reproductive Endocrinology
(Dr. P. Landis Keyes - mentor)

Phone: (919)-515-7224
Fax: (919)-515-4237
Email: john_gadsby@ncsu.edu


Research Area:

The general research focus of our laboratory is to improve our understanding of the control of the development, maintenance and regression of the corpus luteum. Our major animal model is the pig, and was selected for our studies because it displays some unique features and because it is also an economically important species. Our recent projects involve studies of: 1) the control of luteolysis by prostaglandin F2 and their analogs 2) the role of the insulin-like growth factor system in controlling follicular/luteal development and function, and 3) the control of corpus luteum development and function ("luteinization").

1) Control of luteolysis (Refs 1,2,4)

We have shown that PGF2a receptor concentrations on luteal cells increase at a time during the estrous cycle (day 13) when CL's become sensitive to luteolytic actions of PGF2a but no increase occurs in corpora lutea of pregnant/pseudopregnant animals (which have prolonged luteal life-spans), suggesting luteal sensitivity to PGF2a may be a novel mechanism for the maternal recognition of pregnancy.

In other studies, we have been able to significantly induce premature luteolysis and shorten the estrous cycle in gilts by about 5-7 days, with repeated administration of PGF2a analogs. The mechanism underlying this action appears not to be associated with increasing PGF receptor levels, but an inhibition of the luteal insulin-like growth factor system.

2) The role of the insulin-like growth factor system: (Refs,3,5-7)

We have described the expression (at mRNAs and protein levels) of IGF-I, the type IGF-I receptor and IGF-binding proteins 2-5 within the porcine corpus luteum. In particular we have demonstrated that the expression of IGF-I receptor, IGF-I and IGFBP-3 is greatest early in the estrous cycle, suggesting that the IGF-system plays an important (autocrine/paracrine) role in regulating early corpus luteum development and function. Confirming this idea, our in vitro cell culture studies indicate that luteal cells taken during the early luteal phase (days 4 and 7) have a greater steroidogenic response to exogenous IGF-I than those collected at a later stage. Studies are in progress to ascertain the signal transduction pathway of IGF-I's actions on porcine luteal cells and to explore the physiological role of IGF-I using a novel in vivo (ovarian) infusion model. Finally, in collaboration with Dr. Jim Hammond (Hershey Medical Center, Penn State University), we have demonstrated the novel expression of IGF-system components (i.e. acid-labile subunit, mac25 and connective tissue growth factor) within the porcine ovary, which further extend our understanding of how the insulin-like growth factor system may act to control both follicular and luteal development/function in female swine.

3) Control of luteinization

We have begun to explore the regulation of gene expression during luteinization and have isolated some novel gene products based on sequence. Future studies are planned to extend these findings using both in vivo and in vitro models in an attempt to define the role of these novel genes in the process of luteinization.

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Research Tools/Techniques:

In our laboratory we employ a wide variety of techniques which allow us to "view" the corpus luteum, all the way from animal to molecule!

Animal: In vivo studies, ovarian infusion of IGF-system inhibitors/antagonists (including adenovirus constructs).

Tissue/cell: corpus luteum dissociation and luteal cell isolation by centrifugal elutriation, cell culture, histological techniques such as immunocytochemistry, in situ hybridization and apoptosis (Apo-Tag) staining.

Molecule: DNA/RNA analysis using Northern, Southern and slot blots, ribonuclease protection assay, PCR, differential-display PCR, DNA sequencing, DNA-microarray analysis; protein analysis by imunoprecipitation, electrophoresis, Western and ligand-blotting, protein kinase enzyme-activity assays.

Selected Publications:

1) Gadsby, J.E., Balapure, A.K., Britt, J.H. and Fitz, T.A. (1990). PGF2a "receptors" on enzyme-dissociated pig luteal cells throughout the estrous cycle. Endocrinology 126: 787-795.

2) Estill, C.T., Britt, J.H. and Gadsby, J.E. (1993). Repeated administration of prostaglandin F2a during the early luteal phase causes premature luteolysis in the pig. Biol Reprod. 49: 181-185.

3) Gadsby, J.E., Lovdal, J.A., Samaras, S., Barber, J. and Hammond, J.M. (1996). Expression of messenger ribonucleic acids for Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Proteins in porcine corpora lutea. Biol. Reprod. 54: 339-346.

4) Nicholson, W.E., Plotner, D.M., Farin, C.E. and Gadsby, J.E. (1999). Insulin-like growth factor-I, insulin-like growth factor-I receptor and insulin-like growth factor binding protein-3 messenger ribonucleic acids and protein in corpora lutea from prostaglandin F2a-treated gilts. Biol. Reprod. 61: 1527-1534.

5) Wandji, S., Gadsby, J.E., Simmen, F.A., Barber, J.A., and Hammond, J.M. (2000). Messenger ribonucleic acids for mac25 and CTGF are inversely regulated during folliculogenesis and early luteogenesis. Endocrinology 141: 2648-2657.

6) Wandji, S., Gadsby, J.E., Simmen, F.A., Barber, J.A., and Hammond, J.M. (2000). Porcine ovarian cells express messenger ribonucleic acids for the acid-labile subunit and insulin-like growth factor binding protein-3 during follicular and luteal phases of the estrous cycle Endocrinology 141: 2638-2647.

7) Ge, Z., Nicholson, W.E., Plotner, D.M., Farin, C.E. and Gadsby, J.E. (2000). Expression of the messenger ribonucleic acid and protein for insulin-like growth factor-I receptor in porcine corpora lutea . J. Reprod. Fert. 120: 109-114.

Links:

Gadsby Lab Personnel

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