Estrogen-induced hypothalamic synaptic plasticity and pituitary sensitization in the control of the estrogen-induced gonadotrophin surge

Frederick Naftolin, Luis Miguel Garcia-Segura, Tamas L. Horvath, A. Zsarnovszky, Necdet Demir, Ahmed Fadiel, Csaba Leranth, Susanne Vondracek-Klepper, Carole Lewis, Aimee Chang, A. Párducz

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Proper gonadal function requires coordinated (feedback) interactions between the gonads, adenohypophysis, and brain: the gonads elaborate sex steroids (progestins, androgens, and estrogens) and proteins (inhibin-activin family) during gamete development. In both sexes, the brain-pituitary gonadotrophin-regulating interaction is coordinated by estradiol through its opposing actions on pituitary gonadotrophs (sensitization of the response to gonadotrophin-releasing hormone [GnRH]) versus hypothalamic neurons (inhibition of GnRH secretion). This dynamic tension between the gonadotrophs and the GnRH cells in the brain regulates the circulating gonadotrophins and is termed reciprocal/negative feedback. In females, reciprocal/negative feedback dominates ∼90% of the ovarian cycle. In a spectacular exception, the dynamic tension is broken during the surge of circulating estrogen that marks follicle and oocyte(s) maturation. The cause is an estradiol-induced disinhibition of the GnRH neurons that releases GnRH secretion to the highly sensitized pituitary gonadotrophs that in turn release the gonadotrophin surge (the estrogen-induced gonadotrophin surge [EIGS], also known as positive feedback). Studies during the past 4 decades have shown this disinhibition to result from estrogen-induced synaptic plasticity (EISP), including a reversible ∼ 50% loss in arcuate nucleus synapses. The disinhibited GnRH secretion occurs during maximal gonadotroph sensitization and results in the EIGS. Specific immunoneutralization of estradiol blocks the EISP and EIGS. The EISP is accompanied by increases in insulinlike growth factor 1, polysialylated neural cell adhesion molecule, and ezrin, 3 proteins that the authors believe are the links between estrogen-induced astroglial extension and the EISP that releases GnRH secretion at the moment of maximal sensitization of the pituitary gonadotrophs. The result is the paradoxical surge of gonadotrophins at the peak of ovarian estrogen secretion and the triggering of ovulation. This enhanced understanding of the mechanics of gonadotrophin control clarifies elements of the involved feedback loops and opens the way to a better understanding of the neurobiology of reproduction.

Original languageEnglish
Pages (from-to)101-116
Number of pages16
JournalReproductive Sciences
Volume14
Issue number2
DOIs
Publication statusPublished - Feb 2007

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Neuronal Plasticity
Gonadotropins
Estrogens
Gonadotropin-Releasing Hormone
Gonadotrophs
Estradiol
Gonads
Brain
Pituitary Gonadotropins
Neurons
Neural Cell Adhesion Molecules
Activins
Arcuate Nucleus of Hypothalamus
Inhibins
Anterior Pituitary Gland
Neurobiology
Progestins
Menstrual Cycle
Ovulation
Mechanics

Keywords

  • Estradiol
  • Follicle-stimulating hormone
  • GnRH
  • Gonadotrophin feedback
  • Hypothalamus
  • Luteinizing hormone
  • Periventricular area
  • Pituitary
  • Synaptic plasticity

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

Cite this

Estrogen-induced hypothalamic synaptic plasticity and pituitary sensitization in the control of the estrogen-induced gonadotrophin surge. / Naftolin, Frederick; Garcia-Segura, Luis Miguel; Horvath, Tamas L.; Zsarnovszky, A.; Demir, Necdet; Fadiel, Ahmed; Leranth, Csaba; Vondracek-Klepper, Susanne; Lewis, Carole; Chang, Aimee; Párducz, A.

In: Reproductive Sciences, Vol. 14, No. 2, 02.2007, p. 101-116.

Research output: Contribution to journalArticle

Naftolin, F, Garcia-Segura, LM, Horvath, TL, Zsarnovszky, A, Demir, N, Fadiel, A, Leranth, C, Vondracek-Klepper, S, Lewis, C, Chang, A & Párducz, A 2007, 'Estrogen-induced hypothalamic synaptic plasticity and pituitary sensitization in the control of the estrogen-induced gonadotrophin surge', Reproductive Sciences, vol. 14, no. 2, pp. 101-116. https://doi.org/10.1177/1933719107301059
Naftolin, Frederick ; Garcia-Segura, Luis Miguel ; Horvath, Tamas L. ; Zsarnovszky, A. ; Demir, Necdet ; Fadiel, Ahmed ; Leranth, Csaba ; Vondracek-Klepper, Susanne ; Lewis, Carole ; Chang, Aimee ; Párducz, A. / Estrogen-induced hypothalamic synaptic plasticity and pituitary sensitization in the control of the estrogen-induced gonadotrophin surge. In: Reproductive Sciences. 2007 ; Vol. 14, No. 2. pp. 101-116.
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