Alterations in RFamide-related peptide expression are coordinated with the preovulatory luteinizing hormone surge.
The preovulatory LH surge is triggered when the circadian pacemaker, the bilateral suprachiasmatic nucleus (SCN), stimulates the GnRH system in the presence of high estrogen concentrations (positive feedback). Importantly, during the remainder of the estrous cycle, estradiol inhibits LH release via negative feedback. We have recently documented the presence of a novel mammalian RFamide-related peptide (RFRP), a putative gonadotropin-inhibitory hormone (GnIH), that presumably acts upstream of GnRH to modulate the negative feedback effects of estrogen. The present series of studies used female Syrian hamsters to examine the possibility that, in addition to driving the LH surge positively, the SCN concomitantly coordinates the removal of steroid-mediated RFRP inhibition of the gonadotropic axis to permit the surge. We found that the SCN forms close appositions with RFRP cells, suggesting the possibility for direct temporal control of RFRP activity. During the time of the LH surge, immediate-early gene expression is reduced in RFRP cells, and this temporal regulation is estrogen dependent. To determine whether projections from the SCN regulate the timed reduction in activation of the RFRP system, we exploited the phenomenon of splitting. In split animals in which the SCN are active in antiphase, activation of the RFRP system is asymmetrical. Importantly, this asymmetry is opposite to the state of the GnRH system. Together, these findings point to novel circadian control of the RFRP system and potential participation in the circuitry controlling ovulatory function.
Department of Psychology and Helen Wills Neuroscience Institute, 3210 Tolman Hall, 1650, University of California, Berkeley, California 94720-1650, USA.
Erin M
EM
Gibson
Stephanie A
SA
Humber
Sachi
S
Jain
Wilbur P
WP
Williams
Sheng
S
Zhao
George E
GE
Bentley
Kazuyoshi
K
Tsutsui
Lance J
LJ
Kriegsfeld
D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D006224:Cricetinae; D004302:Dorsomedial Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005498:Follicular Phase / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D008029:Lighting; D007986:Luteinizing Hormone / Q000378:metabolism*; D008473:Median Eminence / Q000166:cytology / Q000502:physiology; D008647:Mesocricetus; D008856:Microscopy, Fluorescence; D009434:Neural Pathways; D009479:Neuropeptides / Q000378:metabolism*; D017440:Photoperiod; D010902:Pituitary Gland / Q000166:cytology / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000502:physiology
D004967:Estrogens; D009479:Neuropeptides; C416987:RFamide peptide; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone