, Volume 125, Issue 2, pp 141–145 | Cite as

Chronic GnRH agonist administration down-regulates platelet serotonin transporter in women undergoing assisted reproductive treatment

  • S. Eyal
  • M. Rehavi
  • A. Weizman
  • P. Toren
  • R. Mester
  • Y. Dor
Original Investigation


The effect of pretreatment with the gonadotropin releasing hormone (GnRH) agonistd-Trp6-LHRH (Decapeptyl) on platelet serotonin transporter in women undergoing assisted reproductive treatment (ART) was investigated and compared with women treated with human menopausal gonadotropin (Pergonal). The study group (n=10) was exposed for 12 days to 3.2 mg Decapeptyl C.R. while a comparison group (n=9) was exposed to 11 days of human meno-pausal gonadotropin (Pergonal). All patients were assessed with the Hamilton depression and anxiety scales before and after treatment, and platelet and plasma samples were collected at the same time points. Plasma levels of estradiol, progesterone, FSH and LH were determined by radioimmunoassay (RIA). Platelet serotonin transporter was labeled using high affinity [3H]imipramine binding. The GnRH analogue induced ovarian suppression as reflected by low plasma estradiol levels, while Pergonal administration induced ovarian stimulation. An elevation in the Hamilton depression and anxiety scale scores was observed in the Decapeptyl treated group; this mood alteration was associated with a significant decrease (19%,P<0.05) in the density (Bmax) of platelet [3H]imipramine binding sites. No significant change was observed in the Bmax of the Pergonal treated group. These results indicate that ovarian suppression (menopausal-like state) in young women is associated with depressed and anxious mood and decreased serotonin transporter density.

Key words

GnRH agonist Gonadotropin Depression Anxiety Serotonin transporter Platelets Estradiol Progesterone 


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  1. Amsterdam JD, Winokur A, Mendels J, Caroff S (1979) Effect of gonadotropin-releasing hormone on depressed mood. Lancet ii:1138Google Scholar
  2. Andreyko JL, Marshall LA, Dumesic DA, Jaffe RJ (1988) Therapeutic uses of gonadotropin-releasing hormone analogs. Obstet Gynecol Surv 42:1–21Google Scholar
  3. Bancroft J, Boyle H, Warner P, Fraser HM (1987) The use of an LHRH agonist, buserelin, in the long term management of premenstrual syndrome. Clin Endocrinol 27:171–182Google Scholar
  4. Banks WA, Kastin AJ (1990) Exchange of peptides between the circulation and the nervous system: role of blood-brain barrier. In: Porter JC, Jezova D (eds) Circulating regulatory factors and neuroendocrine function. Plenum Press, New York, pp 56–69Google Scholar
  5. Barrera CM, Kastin AJ, Fasold M, Banks WA (1991) Bidirectional saturable transport of LHRH across the blood-brain barrier. Am J Physiol 261:E312-E318Google Scholar
  6. Biegon A, Reches A, Snyder L, McEwan BS (1983) Serotonergic and noradrenergic receptors in the rat brain: modulation by chronic exposure to ovarian hormones. Life Sci 32:2015–2021Google Scholar
  7. Briley MS, Langer SZ, Raisman R, Sechter D, Zarifan E (1980) Tritiated imipramine binding sites are decreased in platelets of untreated depressed patients. Science 209:303–305Google Scholar
  8. Fernandez-Ruiz JJ, Amor JC, Ramos JA (1989) Time-dependent effects of estradiol and progesterone on the number of striatal dopaminergic D2 receptors. Brain Res 476:388–395Google Scholar
  9. Hammarback S, Backstrome T (1998) Induced unovulation as treatment of premenstrual tension syndrome — double blind crossover study with GnRH-agonist versus placebo. Acta Obstet Gynaecol Scand 67:159–166Google Scholar
  10. Langer SZ, Moret C, Raisman R, Dubocovich ML, Briley M (1980) High-affinity [3H]imipramine binding in rat hypothalamus: association with uptake of serotonin but not of norepinephrine. Science 210:1133–1135Google Scholar
  11. Lesch K-P, Wolozin BL, Murphy DL, Riederer P (1993) Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem 60:2319–2322Google Scholar
  12. Lowry OH, Rosenbrough NJ, Farr AL, Randel RJ (1951) Protein measurement with folin phenol reagent. J Biol Chem 193:265–270Google Scholar
  13. Mora S, Nasello AG, Mandelli-Lopez M, Diaz-Veliz G (1983) LHRH and rat avoidance behavior: influence of castration and testosterone. Physiol Behav 30:19–22Google Scholar
  14. Muse KN, Cetel NS, Futterman LA, Yen SSC (1984) The premenstrual syndrome — effect of “medical ovariectomy”. N Engl J Med 311:1345–1349Google Scholar
  15. Paul SM, Rehavi M, Skolnick P, Goodwin FK (1980) Demonstration of specific “high affinity” binding sites for [3H]imipramine on human platelets. Life Sci 26:953–959Google Scholar
  16. Paul SM, Rehavi M, Skolnick P, Ballenger JC, Goodwin FK (1981) Depressed patients have decreased binding of tritiated imipramine to platelet serotonin “transporter”. Arch Gen Psychiatry 38:1315–1317Google Scholar
  17. Pfaff DW (1973) Luteinizing hormone-releasing factor potentiates lordosis behavior in hypophysectomized ovariectomized female rat. Science 182:1148–1149Google Scholar
  18. Poirier M-F, Benkelfat C, Galzin A-M, Langer SZ (1986) Platelet3H-imipramine binding and steroid hormones serum concentrations during the menstrual cycle. Psychopharmacology 88:86–89Google Scholar
  19. Rehavi M, Paul SM, Skolnick P, Goodwin FK (1980) Demonstration of specific high affinity binding sites for [3H]imipramine on human brain. Life Sci 26:2273–2279Google Scholar
  20. Rehavi M, Specuti H, Weizman A (1987) Upregulation of imipramine binding and serotonin uptake by estradiol in female rat brain. Brain Res 410:135–139Google Scholar
  21. Rosenvaks Z, Davis OK (1990) In vitro fertilization and related techniques. In: Scott JR, Difaia PJ, Hammond CB, Spellacy WN (eds) Danforth's obstetrics and gynecology, 6th edn. J.B. Lippincott, Philadelphia, pp 826–828Google Scholar
  22. Sherwin BB, Suranyi-Cadotte BE (1990) Up-regulatory effect of estrogen on platelet3H-imipramine binding sites in surgically menopausal women. Biol Psychiatry 28:339–348Google Scholar
  23. Weizman A, Morgenstern H, Kaplan B, Amiri Z, Tyano S, Ovadia Y, Rehavi M (1988) Up-regulatory effect of triphasic oral contraceptive on platelet3H-imipramine binding sites. Psychiatry Res 23:23–29Google Scholar
  24. Zorn JR, Barata M, Brami C, Epelboin S, Nathan C, Papageorgiou G, Quantin P, Rolet F, Savale M, Boyer P et al. (1988) Ovarian stimulation for in vitro fertilization combining administration of gonadotropin and blockade of the pituitary withd-Trp6-LHRH microcapsules: pilot study with two protocols. Hum Reprod 3:235–239Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • S. Eyal
    • 1
  • M. Rehavi
    • 1
  • A. Weizman
    • 2
  • P. Toren
    • 3
  • R. Mester
    • 3
  • Y. Dor
    • 4
  1. 1.Department of Physiology and Pharmacology, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  2. 2.Geha Psychiatric Hospital, Felsenstein Medical Research Center, Beilinson Medical Campus and Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Ness-Ziona Psychiatric Hospital, Ness-Ziona and Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  4. 4.IVF Unit, Sheba Medical Center, Tel Hashomer and Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

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