Circadian Rhythms In The Neuroendocrine Dopaminergic Neurons Regulating Prolactin Secretion

Title page for ETD etd-02152005-171515

Type of Document Dissertation
Author Sellix, Michael Timothy
Author's Email Address sellix@neuro.su.edu
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Title CIRC'DI'N R()T(MS IN T(* N*+R,*ND,CRIN*
D,P'MIN*R-IC N*+R,NS R*-+.'TIN- PR,.'CTIN
S*CR*TI,N
Degree PhD
Department /iological Science, Department o
Ad"isory #ommittee Ad"isor !ame Title
Marc *. 0reeman Committee Chair
De1ra '. 0adool Committee Mem1er
0riedrich 2. Stephan Committee Mem1er
Paul 3. Trom1ley Committee Mem1er
Thomas C.S. 2eller III Committee Mem1er
$ey%ords prolactin
hypothalamus
circadian
cloc4 gene
dopamine
rat
Date of Defense #""%!"#!"&
A"aila&ility unrestricted
A&stract
The pituitary gland hormone prolactin 5PR.6 regulates di7erse physiological unctions in the
emale mammal. PR. is secreted into peripheral circulation 1y lactotrophs in the anterior lo1e
o the pituitary gland. The primary physiological regulator o PR. secretion is Dopamine
5D'6. Three populations o neuroendocrine D'ergic neurons 5NDNs6 8ith cell 1odies in the
peri7entricular 5P*9N6 and arcuate 5'RN6 nuclei o the hypothalamus release D'. During
the :!% day estrous cycle o the rat, PR. secretion pea4s on the aternoon o proestrus, due to
a gradual rise in circulating o7arian steroids. *xperiments sho8 that the proestrous aternoon
rise in PR. is timed 1y inputs rom the 1iological cloc4 located in the suprachiasmatic nucleus
5SCN6. Studies 7eriy that disruption o the connection 1et8een SCN and its targets 8ithin the
hypothalamus disrupt the timing o PR. secretion. Recently, it has 1een sho8n that the
oscillatory unction o the SCN occurs due to autoregulatory negati7e eed1ac4 loops o
transcription actor expression 8ithin SCN neurons. These transcription actors are reerred to
as ;cloc4 genes<. Cloc4 genes dri7e cell autonomous oscillations o gene expression and
acti7ity in the SCN and additional areas o the CNS, coordinating rhythms o physiological
acti7ity. -i7en that the timing o PR. secretion appears to 1e regulated 1y the SCN and that
NDNs recei7e direct input rom the SCN, I hypothesi=ed that circadian rhythms o acti7ity in
NDNs time PR. secretion in the o7ariectomi=ed 5,9>6 rat. I ha7e sho8n that NDNs exhi1it
circadian and semi!circadian rhythms o acti7ity that are modulated 1y o7arian steroid
hormones. 0urther, I ha7e determined the light!entrained and ree!running rhythms o cloc4
gene expression in NDNs. In addition, I ha7e ound that antisense 4noc4do8n o se7eral cloc4
genes in the SCN modulates, 1ut ails to a1olish, circadian rhythms o NDN acti7ity. Results
rom these experiments, in agreement 8ith pre7ious 8or4, re7eal that NDNs display circadian
and semi!circadian rhythms o D' release, dri7en 1y direct inluence rom the SCN. My
results suggest a unctional lin4 1et8een the expression o cloc4 genes 8ithin SCN neurons
and NDNs in the control o circadian rhythms o D' release and PR. secretion in the emale
mammal.