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6.10:

๋‚ด๋ถ„๋น„ ์‹ ํ˜ธ์ „๋‹ฌ

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Endocrine Signaling

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๋‚ด๋ถ„๋น„ ์‹ ํ˜ธ๋Š”๊ฐ๊ธฐ ๋‹ค๋ฅธ ์ƒ์ฒด ๊ธฐ๊ด€์— ์œ„์น˜ํ•ด ์žˆ๋Š” ์„ธํฌ๋“ค์ด์„œ๋กœ ์˜์‚ฌ์†Œํ†ต์„ ํ•ด์•ผ ํ•  ๋•Œ ๋ฐœ์ƒํ•ฉ๋‹ˆ๋‹ค์˜ˆ๋ฅผ ๋“ค์–ด ๋‡Œํ•˜์ˆ˜์ฒด๊ฐ€์‹ ์žฅ๊ณผ ์˜์‚ฌ์†Œํ†ต์„ ํ•  ๋•Œ ๋ฐœ์ƒํ•˜๋Š” ๊ฒƒ์ด์ฃ ๋‚ด๋ถ„๋น„ ์‹ ํ˜ธ๊ฐ€ ๋ฐœ์ƒํ•  ๋•Œ, ์‹ ํ˜ธ ๋ฐฐ์œ„์ž์ธ ํ˜ธ๋ฅด๋ชฌ์€ํ˜ˆ์•ก์˜ ํ๋ฆ„์„ ์ด์šฉํ•ด ๋ชฉํ‘œ ์„ธํฌ์— ๋„๋‹ฌํ•ฉ๋‹ˆ๋‹ค์˜ˆ๋ฅผ ๋“ค์–ด, ๋‡Œํ•˜์ˆ˜์ฒด๊ฐ€ ์‹ ์žฅ์—๊ฒŒ ์†Œ๋ณ€์œผ๋กœ๋ถ€ํ„ฐ์ˆ˜๋ถ„ ์žฌํก์ˆ˜ ์‹ ํ˜ธ๋ฅผ ๋ณด๋‚ผ ๋•Œ์•„๋ฅด๊ธฐ๋‹Œ ๋ฐ”์†Œํ”„๋ ˆ์‹ , ํ˜น์€ AVP๋ฅผํ˜ˆ์•ก์œผ๋กœ ํ˜๋ ค ๋ณด๋ƒ…๋‹ˆ๋‹คํ˜ˆ์•ก์ด ์‹ ์žฅ์—์„œ ์—ฌ๊ณผ ๋  ๋•Œ,AVP๋Š” ๋ชฉํ‘œ ์‹ ์žฅ ์„ธํฌ์—์„œG ๋‹จ๋ฐฑ์งˆ๊ฒฐํ•ฉ์ˆ˜์šฉ์ฒด์ธ AVPR2์™€ ๊ฒฐํ•ฉํ•ฉ๋‹ˆ๋‹คํ˜ธ๋ฅด๋ชฌ์ด ์ž‘์šฉ์„ ํ•จ๊ณผ ๋™์‹œ์—G ๋‹จ๋ฐฑ์งˆ ์†Œ๋‹จ์œ„์ฒด๋Š” ์ˆ˜์šฉ์ฒด์™€ ๋–จ์–ด์ ธ์•„๋ฐ๋‹์‚ฐ ๊ณ ๋ฆฌํ™” ํšจ์†Œ๋ฅผ ํ™œ์„ฑํ™” ์‹œ์ผœ๋‘ ๋ฒˆ์งธ ๋ฉ”์‹ ์ ธ์ธ ์‚ฌ์ดํด๋ฆญ AMP๋ฅผ ์ƒ์„ฑํ•ฉ๋‹ˆ๋‹ค์‚ฌ์ดํด๋ฆญ AMP๋Š” ๋‹จ๋ฐฑ์งˆ ํ‚ค๋‚˜์•„์ œ A, ํ˜น์€ PKA๋ฅผ ํฌํ•จํ•˜์—ฌ์„ธํฌ ๋‚ด ์ˆœ์ฐจ์  ๋ฐ˜์‘์„ ์ผ์œผํ‚ต๋‹ˆ๋‹คPKA๋Š” ๋‘ ๊ฐ€์ง€ ๊ธฐ๋Šฅ์„ ๊ฐ€์ง€๊ณ  ์žˆ์Šต๋‹ˆ๋‹ค์ฒซ ๋ฒˆ์งธ๋กœ PKA๋Š” ์„ธํฌ์งˆ ์†Œํฌ ๋‚ด์— ์ €์žฅ๋œ์•„์ฟ ์•„ํฌ๋ฆฐ ํ†ต๋กœ์ธ APQ2๋ฅผ ์ธ์‚ฐํ™” ์‹œํ‚ต๋‹ˆ๋‹ค์ด ๊ณผ์ •์€ ์†Œํฌ์™€ ํ†ต๋กœ๋ฅผ์„ธํฌ ๋ง‰์œผ๋กœ ์˜ฎ๊ฒจ์ˆ˜๋ถ„์ด ์‹ ์žฅ ์„ธํฌ ์•ˆ์ชฝ์œผ๋กœ ๋‹ค์‹œ ๋˜๋Œ์•„ ์˜ค๊ฒŒ ํ•ฉ๋‹ˆ๋‹ค๋‘ ๋ฒˆ์งธ๋กœ PKA๋Š” ์„ธํฌํ•ต ๋‚ด์˜ CREB๋ฅผ ์ธ์‚ฐํ™” ์‹œ์ผœ์•„์ฟ ์•„ํฌ๋ฆฐ 2 ์œ ์ „์ž์— ๊ฒฐํ•ฉ์ด ๋˜์–ด์ „์‚ฌ๋ฅผ ์‹œ์ž‘ํ•˜๊ณ ๊ทธ ํ›„ ์ƒˆ๋กœ์šด ์•„์ฟ ์•„ํฌ๋ฆฐ ํ†ต๋กœ๋กœ ๋ฒˆ์—ญ์ด ๋ฉ๋‹ˆ๋‹ค๋”ฐ๋ผ์„œ, ๋‚ด๋ถ„๋น„ ์‹ ํ˜ธ๋Š”์„œ๋กœ ๋–จ์–ด์ ธ ์žˆ๋Š” ์„ธํฌ๋“ค์ด ๋ฐ˜๋“œ์‹œ ์˜์‚ฌ์†Œํ†ต์„ ํ•ด์•ผ ํ•˜๋Š”์‚ผํˆฌ์กฐ์ ˆ๊ณผ ์—ฌํƒ€ ๊ธฐ๋Šฅ๋“ค์—์„œ ํ•ต์‹ฌ์ ์ธ ๋‹จ๊ณ„์ž…๋‹ˆ๋‹ค

6.10:

๋‚ด๋ถ„๋น„ ์‹ ํ˜ธ์ „๋‹ฌ

๋‚ด๋ถ„๋น„ ์„ธํฌ(endocrine cell)๋Š” ๋‹ค๋ฅธ ์žฅ๊ธฐ์— ์žˆ๋Š” ํ‘œ์  ์„ธํฌ(target cell)์™€ ์†Œํ†ตํ•˜๋Š” ํ˜ธ๋ฅด๋ชฌ์„ ์ƒ์‚ฐํ•ฉ๋‹ˆ๋‹ค. ํ˜ธ๋ฅด๋ชฌ์€ ์ˆœํ™˜๊ณ„(circulatory system)๋ฅผ ํ†ตํ•ด ๋‹ค๋ฅธ ์žฅ๊ธฐ๋กœ ์ด๋™ํ•ฉ๋‹ˆ๋‹ค, ์ด๋•Œ ํ˜ธ๋ฅด๋ชฌ์ด ์ง€๋‚˜๊ฐ€๋Š” ๋ชจ๋“  ์ž๋ฆฌ๊ฐ€ ํ˜ธ๋ฅด๋ชฌ์— ๋…ธ์ถœ๋˜์ง€๋งŒ ํ˜ธ๋ฅด๋ชฌ ์ˆ˜์šฉ์ฒด(hormone receptor)๋ฅผ ๋ฐœํ˜„ํ•˜๋Š” ์„ธํฌ์™€ ํ‘œ์  ์„ธํฌ๋งŒ ํ˜ธ๋ฅด๋ชฌ์˜ ์˜ํ–ฅ์„ ๋ฐ›์Šต๋‹ˆ๋‹ค. ๋‚ด๋ถ„๋น„ ์‹ ํ˜ธ์ „๋‹ฌ(endocrine signaling)์€ ํ‘œ์  ์„ธํฌ์—์„œ ๋Š๋ฆฐ ๋ฐ˜์‘์„ ์œ ๋ฐœํ•˜์ง€๋งŒ, ๋Œ€์‹  ์ด ํšจ๊ณผ๊ฐ€ ์˜ค๋ž˜ ์ง€์†ํ•ฉ๋‹ˆ๋‹ค.

๋‚ด๋ถ„๋น„ ์ˆ˜์šฉ์ฒด์—๋Š” ์„ธํฌ ํ‘œ๋ฉด ์ˆ˜์šฉ์ฒด(cell surface receptor)์™€ ์„ธํฌ ๋‚ด ์ˆ˜์šฉ์ฒด(intracellular receptor) ๋‘ ์ข…๋ฅ˜๊ฐ€ ์žˆ์Šต๋‹ˆ๋‹ค. ์„ธํฌ ํ‘œ๋ฉด ์ˆ˜์šฉ์ฒด๋Š” ๋‹ค๋ฅธ ๋ง‰๊ฒฐํ•ฉ ์ˆ˜์šฉ์ฒด(membrane bound receptor)์™€ ์œ ์‚ฌํ•˜๊ฒŒ ์ž‘์šฉํ•ฉ๋‹ˆ๋‹ค. ๋ฆฌ๊ฐ„๋“œ(ligand)์ธ ํ˜ธ๋ฅด๋ชฌ์€ ํŠน์ •ํ•œ G-๋‹จ๋ฐฑ์งˆ ๊ฒฐํ•ฉ ์ˆ˜์šฉ์ฒด(G-protein coupled receptor)์™€ ๊ฒฐํ•ฉํ•ฉ๋‹ˆ๋‹ค. ๊ทธ๋Ÿฌ๋ฉด ์ˆ˜์šฉ์ฒด์— ํ˜•ํƒœ์ ์ธ ๋ณ€ํ™”(conformational change)๊ฐ€ ์‹œ์ž‘๋˜๊ณ , G-๋‹จ๋ฐฑ์งˆ์˜ ๋‹จ์œ„์ฒด๊ฐ€ ๋ฐฉ์ถœ๋ฉ๋‹ˆ๋‹ค. ๋ฐฉ์ถœ๋œ ๋‹จ๋ฐฑ์งˆ์€ ์‹ ํ˜ธ ์—ฐ์‡„๋ฐ˜์‘(signaling cascade)๊ณผ ์ „์‚ฌ ์ธ์ž(transcription factor)๋ฅผ ์ด‰๋ฐœํ•˜์—ฌ ์„ธํฌ ์™ธ๋ถ€ ์‹ ํ˜ธ๋ฅผ ๋‚ด๋ถ€ํ™”ํ•˜๋Š” 2์ฐจ ์ „๋‹ฌ์ž(second messenger)๋ฅผ ํ™œ์„ฑํ™”ํ•ฉ๋‹ˆ๋‹ค.

๋งŽ์€ ํ˜ธ๋ฅด๋ชฌ์€ ์—ํ”ผ๋„คํ”„๋ฆฐ(epinephrine), ๋…ธ๋ฅด์—ํ”ผ๋„คํ”„๋ฆฐ(norepinephrine), ์ธ์Š๋ฆฐ(insulin), ํ”„๋กœ์Šคํƒ€๊ธ€๋ž€๋”˜(prostaglandin), ํ”„๋กœ๋ฝํ‹ด(prolactin), ์„ฑ์žฅ ํ˜ธ๋ฅด๋ชฌ๊ฐ™์ด ์„ธํฌ ํ‘œ๋ฉด ์ˆ˜์šฉ์ฒด๋ฅผ ํ†ตํ•ด ์ž‘์šฉํ•ฉ๋‹ˆ๋‹ค.

ํ…Œ์Šคํ† ์Šคํ…Œ๋ก (testosterone), ์—์ŠคํŠธ๋กœ๊ฒ(estrogen; ์—์ŠคํŠธ๋กœ์  ), ํ”„๋กœ๊ฒŒ์Šคํ…Œ๋ก (progesterone; ํ”„๋กœ์ œ์Šคํ…Œ๋ก )๊ณผ ๊ฐ™์€ ์Šคํ…Œ๋กœ์ด๋“œ(steroid) ํ˜ธ๋ฅด๋ชฌ์€ ์„ธํฌ ๋‚ด ์ˆ˜์šฉ์ฒด๋ฅผ ์‚ฌ์šฉํ•˜์—ฌ ์‹ ํ˜ธ๋ฅผ ์ „๋‹ฌํ•ฉ๋‹ˆ๋‹ค. ์ด ํ˜ธ๋ฅด๋ชฌ์€ ์ž‘์€ ์†Œ์ˆ˜์„ฑ(hydrophobic) ๋ถ„์ž์ด๊ธฐ ๋•Œ๋ฌธ์— ์™ธ๋ถ€ ์„ธํฌ๋ง‰์„ ๋ฐ”๋กœ ํ†ต๊ณผํ•ฉ๋‹ˆ๋‹ค. ํ•ด๋‹น ์„ธํฌ๊ฐ€ ํ‘œ์  ์„ธํฌ์ผ ๊ฒฝ์šฐ ํ˜ธ๋ฅด๋ชฌ์€ ์„ธํฌ ์•ˆ์—์„œ ์ˆ˜์šฉ์ฒด์— ๊ฒฐํ•ฉํ•ฉ๋‹ˆ๋‹ค. ์ด ๊ฒฐํ•ฉ์€ ์ˆ˜์šฉ์ฒด์— ํ˜•ํƒœ์ ์ธ ๋ณ€ํ™”๋ฅผ ์ผ์œผ์ผœ ์ˆ˜์šฉ์ฒด๊ฐ€ ์ž ์žฌ์ ์œผ๋กœ ์ „์‚ฌ ์ธ์ž๋กœ์„œ ํ™œ๋™ํ•  ์ˆ˜ ์žˆ๊ฒŒ ํ™œ์„ฑํ™”ํ•ฉ๋‹ˆ๋‹ค. ์ด๋ ‡๊ฒŒ ํ™œ์„ฑํ™”ํ•œ ์ˆ˜์šฉ์ฒด ๋˜๋Š” ํ˜ธ๋ฅด๋ชฌ-์ˆ˜์šฉ์ฒด ๋ณตํ•ฉ์ฒด(hormone-receptor complex)๋Š” ์œ ์ „์ž ๋ฐœํ˜„์„ ์ด‰์ง„ํ•˜๊ฑฐ๋‚˜ ์–ต์ œํ•ฉ๋‹ˆ๋‹ค.

์„ธํฌ ๋‚ด ํ˜ธ๋ฅด๋ชฌ ์ˆ˜์šฉ์ฒด๋Š” ๊ด‘๋ฒ”์œ„ํ•œ ์ˆ˜์šฉ์ฒด ์ƒ๊ณผ(superfamily)์ด์ง€๋งŒ ๊ณตํ†ต์ ์œผ๋กœ ์„ธํฌ ๋‚ด ํ˜ธ๋ฅด๋ชฌ ์ˆ˜์šฉ์ฒด๋Š” ์„ธ ๊ฐœ์˜ ๋‹จ๋ฐฑ์งˆ ๋„๋ฉ”์ธ(protein domain)์„ ๊ฐ€์ง„ ๋‹จ์ผ ํด๋ฆฌํŽฉํƒ€์ด๋“œ(polypeptide) ์‚ฌ์Šฌ์ž…๋‹ˆ๋‹ค. N-๋ง๋‹จ์—๋Š” ํ™œ์„ฑ ์ „์‚ฌ ์ธ์ž ๋„๋ฉ”์ธ(active transcription factor domain)์ด ์žˆ์Šต๋‹ˆ๋‹ค. ๊ฐ€์šด๋ฐ์—๋Š” ํŠน์ • ์œ ์ „์ž์— ๊ฒฐํ•ฉํ•˜๋Š” DNA ๊ฒฐํ•ฉ ๋„๋ฉ”์ธ(DNA binding domain)์ด ์žˆ์Šต๋‹ˆ๋‹ค. ๊ทธ๋ฆฌ๊ณ  C-๋ง๋‹จ์—๋Š” ํ˜ธ๋ฅด๋ชฌ์ด ๊ฒฐํ•ฉํ•˜๋Š” ๋„๋ฉ”์ธ์ด ์žˆ์Šต๋‹ˆ๋‹ค.

Suggested Reading

Iliodromiti, Zoe, Nikolaos Antonakopoulos, Stavros Sifakis, Panagiotis Tsikouras, Angelos Daniilidis, Kostantinos Dafopoulos, Dimitrios Botsis, and Nikolaos Vrachnis. “Endocrine, Paracrine, and Autocrine Placental Mediators in Labor.” Hormones (Athens, Greece) 11, no. 4 (December 2012): 397–409. [Source]

Mayer, Emeran A., Rob Knight, Sarkis K. Mazmanian, John F. Cryan, and Kirsten Tillisch. “Gut Microbes and the Brain: Paradigm Shift in Neuroscience.” Journal of Neuroscience 34, no. 46 (November 12, 2014): 15490–96. [Source]