Behavioral Neuroscience, lecture on GnRH
LORDOSIS
X. GnRH (Gonadotropin-Releasing Hormone)
A. GnRH is a decapeptide (10 aa; also called LHRH or luliberin)
cleaved from a 92 aa preprohormone
1. 14 known forms: lGnRH1,2,3, dfGnRH, cfGnRH, sGnRH1,2,
sbGnRH, cGnRH1,2, mGnRH
a. named for discovery in lamprey, dogfish, catfish, salmon,
sea bream, chicken, and mammals
i. all vertebrates have cGnRH2 (may be ancestral)
2. GnIH = GnRIH discovered in fish and birds
B. GnRH cells develop from neural ridges that give rise to
olfactory epithelium and posterior hypothalamic neural ridge
1. migration from olfactory bulb to POA
2. cGnRH2 is a neuromodulator found in VMN,
olfactory bulb, medial septum, diagonal band of Broca,
mPOA, SCN and hippocampus
a. GnRH made in VMN and released in the midbrain central grey
stimulates sexual behavior
i. also GnRH projections to Habenula, BNST and Amygdala
3. Hormonal GnRH (usually sGnRH1, mGnRH or cGnRH1: 1/species)
made in the arcuate mediobasal nuclei and preoptic nuclei
a. colocalize galanin
C. GnRH release is stimulated by NE from the locus ceruleus
and leptin from adipose cells
1. inhibited by b-endorphin, also CRH, ACTH, B/F
D. Type I receptors on gonadotropic cells of the pituitary, but also in
dorsal hippocampus, amygdala, septum, and subiculum
1. 2nd messengers: Gs /AC /cAMP + IP3 /DG /Ca++
2. stimulates release of both LH and FSH
a. pulsatile release necessary for gonadotropin secretion
i. autopriming ® LH/FSH release
4-6X higher on 2nd dosage of GnRH
ii. pulsatility also maintains [GnRH-R]
ii. pulses derived from oscillatory ARC cells paced by
SCN transmitters like NPY, GABA and Glu, plus NE + NO
iii. and from ultrashort positive feedback
(1) pacemaker ® V gated Ca++® + GnRH ® + IP3/Ca++
(2) Ca++ ® + NOS ® + NO ® + GnRH
b. preovulatory surge of GnRH stimulated by Glu, NE
i. timed/inhibited by b-endorphin
E. Preovulatory surge in GnRH predicts/precedes Lordosis by causing
LH surge and increased P
1. increased P disinhibits (via 5-HT) GnRH release in MCG