1. GnRH-I AND II INDUCED EFFECTS IN HUMAN OVARIAN CELLSBy
In Sun, Hong
Reproductive and Developmental Science program
Department of Obstetrics and Gynecology
The University of British Columbia

2. Hypothalamus connecting to the pituitary gland which sends hormonal signals to the rest of the body
Richard Bertram et al. (2006), Scholarpedia, 1(12):1330

3. Neural control of reproduction
G. W. HARRIS
(1913–1971)

4. The identity of Gonadotropin-releasing hormone
Roger Guillemin
The Nobel Prize in Physiology or Medicine 1977
Andrew V. Schally
The identity of GNRH1 was clarified by the 1977 Nobel Laureates Roger Guillemin and Andrew V. Schally

5. GnRH regulate gonadotropin and hormone secretion
Nature Neuroscience 7, (2004)

6. Structure of GnRH and its receptor
J Clin Endocrinol Metab 57: 62, 1983

7. The identity of GnRH in extra-pituitary tissues
Exp Biol Med (Maywood) Feb;233(2): Review
Peter C.K Leung
“GnRH has been implicated as an autocrine regulator in several extra-pituitary tissues, including the ovary and placenta”

8. Clinical application of GnRH and its analogues
Gonadal regulation
IVF Therapy
Cancer Therapy

9. Gonadotropin-releasing hormone agonists in the treatment of various cancers

10. Human cancer tissues reported to express GnRH-R
Endocr Rev Oct;33(5):

11. Anti proliferative activity of GnRH
Breast cancer cells
Ovarian cancer cells
Endocrine Dec;13(3):
Endocrinology Nov;142(11):
Prostate cancer cells
Endometrial cancer cells
Cancer Res Aug 1;54(15):4091-5
Eur J Endocrinol Jan;146(1):1-14

12. Anti-metastatic activity of GnRH
Front Neuroendocrinol Dec;24(4):
Int J Oncol Aug;33(2):405-13
Int J Cancer Jun 1;99(4):505-13

13. Anti-angiogenic activity of GnRH
Endocrinology Oct;151(10):

14. Anti-tumor activity through growth factor interfering
Endocr Rev Oct;33(5):

15. Tumor GnRH-R as a Molecular Target for Novel Therapeutic Strategies in Cancers
Endocr Rev Oct;33(5):

16. Ovarian stimulation with GnRH agonist during IVF therapy

17. Estimated risk of Down syndrome according to maternal age
Br J Obstet Gynaecol 1997; 94:
Regulated fertility services: a commissioning aid –
June 2009, from the Department of Health UK

18. The decreasing follicle pool and age related decline in fertility
Am J Obstet Gynecol 110:746, 1971
Endocr Rev 18:71, 1997

19. Ovarian stimulation with GnRH agonist

21. What is the functional role and molecular mechanism of GnRH-I and II in human granulosa cells?

22. The structure and function of ovarian follicles
Mol Cell Endocrinol Dec 30;228(1-2):67-78.

23. After two weeks of sv40 large T antigen transfection
Transfected rapidly
growing colony
Untransfected granulosa cells

24. The presence of SV40 large T antigen in transfected colonies

25. The characteristics of primary cultured granulosa cells and immortalized granulosa cell lines

26. Anti-proliferative effects of GnRH-I or II on human granulosa cells

27. Apoptotic effects of GnRH-I or II on human granulosa cells
GnRH II
Antide

28. GnRH-I or II exert anti-proliferative effects on human granulosa cells by interfering with the IGF-I activity

29. The attenuating effects of GnRH-I or II on the activity of IGF-I in granulosa cells apoptosis

30. GnRH-I or II interfere with IGF-I induced Akt signaling pathways

31. GnRH-I or II interfere with IGF-I induced Akt signaling pathways

32. 1 2 Two possible mechanisms of GnRH-I or II induced anti-proliferative
effects in human granulosa cells 1 2
GnRH-I, II
GnRH-I, II
IGF-I
Caspase-dependent pathway
Akt
Apoptosis
IGF-I activity

33. Acknowledgements: Dr. Leung’s Lab Dr. Peter CK Leung
Dr. Christian Klausen
Jordan Cheng
Raymond Lau
Kelvin So
William Chang
Mya Zhang