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KMID : 0894520090130040257
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Development & Reproduction
2009 Volume.13 No. 4 p.257 ~ p.264
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Effect of 6-Hydroxydopamine (6-OHDA) on the Expression of Hypothalamus-Pituitary Axis Hormone Genes in Male Rats
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Heo Hyun-Jin
Ahn Ryun-Sup
Lee Sung-Ho
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Abstract
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A neurotoxin, 6-hydroxydopamine (6-OHDA) has been widely used to create animal model for Parkinson’s disease (PD) due to its specific toxicity against dopaminergic (DA) neurons. Since DA signals modulate a broad spectrum of CNS physiology, one can expect profound alterations in neuroendocrine activities of both PD patients and 6-OHDA treated animals. Limited applications of 6-OHDA injection model, however, have been made on the studies of hypothalamuspituitary neuroendocrine circuits. The present study was performed to examine whether blockade of brain catecholamine (CA) biosynthesis with 6-OHDA can make any alteration in the transcriptional activities of hypothalamus-pituitary hormone genes in adult male rats. Three-month-old male rats (SD strain) were received 6-OHDA (200 ㎍ in 10 ㎕ of saline/animal) by intracerebroventricular (icv) injection, and sacrificed after two weeks. To determine the mRNA levels of hypothalamuspituitary hormone genes, total RNAs were extracted and applied to the semi-quantitative RT-PCRs. The mRNA levels of tyrosine hydroxylase (TH), the rate-limiting enzyme for the catecholamine biosynthesis, were significantly lower than those from the control group (control:6-OHDA=1:0.72±0.02AU, p＜0.001), confirming the efficacy of 6-OHDA injection. The mRNA levels of gonadotropin-releasing hormone (GnRH) and corticotropin releasing hormone (CRH) in the hypothalami from 6-OHDA group were significantly lower than those from the control group (GnRH, control:6-OHDA=1:0.39±0.03AU, p＜0.001; CRH, control:6-OHDA=1:0.76±0.07AU, p＜0.01). There were significant decreases in the mRNA levels of common alpha subunit of glycoprotein homones (Cgα), LH beta subunit (LH-β), and FSH beta subunit (FSH-β) in pituitaries from 6-OHDA group compared to control values (Cgα, control:6-OHDA=1:0.81±0.02AU, p＜0.001; LH-β, control:6-OHDA=1:0.68±0.04AU, p＜0.001; FSH-β, control:6-OHDA=1:0.84±0.05AU, p＜0.001). Similarly, the level of adrenocorticotrophic hormone (ACTH) transcripts from 6-OHDA group was significantly lower than that from the control group (control: 6-OHDA=1:0.86±0.04AU, p＜0.01). The present study demonstrated that centrally injected DA neurotoxin could downregulate the transcriptional activities of the two hypothalamus-pituitary neuroendocrine circuits, i.e., GnRH-gonadotropins and CRH-ACTH systems. These results suggested that hypothalamic CA input might affect on the activities of gonad and adrenal through modulation of hypothalamus-pituitary function, providing plausible explanation for frequent occurrence of sexual dysfunction and poor stress-response in PD patients.
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KEYWORD
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6-OHDA, Hypothalamus-pituitary axis, GnRH-gonadotropins, CRH-ACTH, Parkinson’s disease
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