8/12/2019 Circadian Rhythms in the Neuroendocrine Dopaminergic Neurons Regulating Prolactin Secretion

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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

U! etd!"#$%#""%!$&$%$%

Title CIRC'DI'N R()T(MS IN T(* N*+R*NDCRIN*

DP'MIN*R-IC N*+RNS R*-+'TIN- PR'CTIN

S*CR*TIN

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 5PR6 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 thehypothalamus 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

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transcription actor expression 8ithin SCN neurons. These transcription actors are reerred to

as ;cloc4 genes6 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.