Hypothalamic-anterior pituitary-peripheral gland axis system下視丘-腦下垂體前葉-周邊腺體軸賀爾蒙系統

[[內分泌系統]]

許多內分泌系統中的荷爾蒙都是由負反饋系統所控制，例如腎上腺分泌的糖皮質激素就是如此。下視丘分泌促肾上腺皮质素释放素(CRH)，CRH會使腦下垂體分泌促腎上腺皮質素(ACTH)，而ACTH會使腎上腺分泌糖皮質激素，如皮質醇。糖皮質激素不但會使身體有對應的反應外，也會使下視丘和腦下垂體的分泌減少，因此只要糖皮質激素已經到達一定的量，就不會再繼續分泌。

主條目:內分泌系統、Central nervous system中樞神經系統CNS

神經系統的下視丘接受身體的神經訊息傳入，藉由賀爾蒙控制腦下腺而影響周邊內分泌腺體。連結神經系統和內分泌系統的器官。

[神經]分泌，[透過血液，到達目標細胞的接受器與之結合。所以沒有接受器的不算是賀爾蒙]。就稱做[神經賀爾蒙]，譬如所有的[下視丘賀爾蒙](參考Hypothalamic-anterior pituitary-peripheral gland axis system下視丘-腦下垂體前葉-周邊腺體軸賀爾蒙系統和ADH、oxytocin)。

Hypothalamus下視丘 分泌hypophysiotropic hormone (促腦下腺素) 腦下腺控制賀爾蒙 下視丘賀爾蒙(Hypothalamic Hormones) ~tropin Releasing hormone 釋放激素RH Inhibiting hormone 抑制激素IH H寫F亦可 Hormone1	Pituitary gland腦下腺(hypophysis腦下垂體)前葉 分泌腦下腺前葉賀爾蒙(anterior Pituitary Hormones) 分成basophil cell嗜鹼性細胞, chromophobe cell嫌色细胞, acidophil cell嗜酸性細胞, ~troph分泌Hormone2 ~tropin 促(腺體)素 ~tropic Hormone X gland stimulating Hormone XSH   X腺刺激激素 對Hormone1有負回饋機制		Peripheral gland周邊腺體 分泌Hormone3 對Hormone1和Hormone2有負回饋機制	Target目標器官
Thyrotropin releasing hormone 促甲狀腺素釋放激素TRH	basophil cell嗜鹼性細胞,	thyrotroph分泌 thyrotropin 促甲狀腺素 thyrotropic Hormone Thyroid-stimulating Hormone TSH   甲狀腺刺激激素	Thyroid gland分泌 Thyroxine(t4) Triiodothyronine(t3)	Target目標器官
Gonadorelin =Gonadotropin releasing hormone 促性腺(素)釋放激素GnRH Ex. LH-RH		gonadotroph分泌 gonadotropin 促性腺素 gonadotropic Hormone FSH: follicle-stimulating Hormone 濾泡刺激激素 LH: luteinizing hormone黃體生成素,在男性又稱作間質細胞刺激激素ICSH(interstitial cell stimulating hormone) hCG 效果同LH,懷孕時取代LH	Gonads性腺 Ovaries卵巢 Testis睪丸 Testosterone睪固酮 Progesterone黃體素(助孕酮) Estrogen動情素	Target目標器官
Corticotropin releasing hormone 促腎上腺皮質(素)釋放激素CRH	chromophobe cell嫌色细胞,	corticotroph分泌 corticotropin corticotropic Hormone adrenocorticotropic hormone 促腎上腺皮質素ACTH 和 Melanocyte-stimulating Hormone MSH   黑色素細胞刺激激素	Adrenocortex腎上腺皮質 Cortisol皮質醇 葡萄糖皮質類固醇 MSH Melanocye黑色素細胞(分泌melanin黑色素) ACTH長得像MSH，所以愛迪生氏症(corticoids少)會使得ACTH分泌變多，而使得melanocyte以為MSH變多，而分泌更多黑色素而使得皮膚變黑，譬如甘迺迪總統。 MSH和腦部受體的結合與癌症等疾病晚期的惡病質（Cachexia）有關係。	Target目標器官 ACTH和MSH來自同preprohormone
Growth hormone releasing hormone生長激素釋放激素GHRH Growth hormone inhibiting hormone 生長激素抑制激素GHIH=somatostatin 體抑素	acidophil cell嗜酸性細胞,	somatotroph分泌 somatotropin somatotropic Hormone (Human) growth hormone (人類)生長激素(h)GH	Liver to secrete somatomedin (insulin-like growth factor類胰島素生長因子, IGF-1), IGF-2	Target目標器官
Prolactin inhibiting factor/hormone泌乳素抑制因子PIF/PIH =dopamine多巴胺DA		lactotroph分泌 Lactotropin=prolactin泌乳素PRL		Target目標器官
其他地方相同原理的調節系統
胃腸道中有攝食的葡萄糖glc	Intestine secrete GIP(glucose-dependent insulinotropic peptide葡萄糖依賴性促胰島素胜肽)		Pancreas beta-cell secrete insulin胰臟的beta細胞分泌胰島素	Target目標器官: 葡萄糖進入其他器官和靜止的肌肉
RAAS renin腎素酵素把肝分泌的angiotensinogen 轉成angiotensin I	血管收縮素/血管張力素Angiotensin I被酵素ACE變成angiotensin II		Adrenocortex腎上腺皮質分泌aldosterone醛固酮/留鹽激素礦物性皮質類固醇	Target目標器官 腎、大腸、汗腺
三級神經元third-order neuron Ex. brain	二級神經元second-order neuron Ex. Spinal cord		一級神經元first-order neuron Ex. Nerve	Target目標器官
CNS	ENS		胃腸道

下視丘分泌激素(posterior pituitary hormone)儲存在腦下腺後葉(神經垂體):

分泌oxytoxin催產素和ADH抗利尿激素(Anti-diuretic hormone (also called vasopressin血管加壓素))

感覺神經:一級、二級、三級

運動神經:下運動、上運動神經

國立陽明大學施承典博士老師 教授，吳宗頴藥師整理

acidophil cell的應用

pituitary gland的somatotroph和lactotroph同樣為acidophil cell

所以青春期的時候，GH作用在乳房，連男生也會有乳頭敏感的現象

另外長得像dopamine的麥角生物鹼，可以作用在somatotroph抑制somatotrophin的分泌而治療巨人症

下視丘賀爾蒙

產生釋放激素，調控腦垂線激素的分泌

生長激素釋素 (GHRH)

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生長激素抑素

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促腎上腺皮質素釋素 (CRH)

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甲狀腺促素釋素 (TRH)

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促性腺素釋素 (GnRH)

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腦垂腺(前葉)賀爾蒙

生長激素 (GH)

促進生長發育 巨人症 侏儒症

促甲狀腺素 (TSH)

促進甲狀腺分泌

促腎上腺皮質素 (ACTH)

促進腎上腺皮質分泌

促濾泡成熟素 (FSH)

與生殖有關的激素

黃體成長素 (LH)

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Hypothalamic-pituitary-adrenal axis (HPA axis)下視丘-腦下腺前葉-腎上腺軸

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Hypothalamic–pituitary–gonadal axis (HPG axis)下視丘-腦下腺前葉-性腺軸

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Hypothalamic–pituitary–thyroid axis (HPT axis)下視丘-腦下腺前葉-甲狀腺軸

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各賀爾蒙的臨床適應症

Somatotropin	GH deficiency p.646 Prader-Willi syndrome Turner syndrome Chronic renal failure in pediatric patient Small-for-gestational-age condition at birth in which the child has fail to catch up by age 2 p. 647
	Idiopathic short stature p.647 Non-hormone-deficient short stature
	Servere catabolic state Ex. Wasting in AIDS patients p.647
	Patient of short bowel syndrome depending on TPN p.647
	Anti-aging X p.647
	Banned drug of Olympic p.647
	Antiobesity drug X p.648
	Bovine milk production p.649
IGF-1 mecasermin	IGF-1 deficiency not responsive to GH
Somatostatin and Octreotide and lanreotide(long-acting)	Small pituitary adenoma
GH receptor antagonist Pegvisomant
D2 agonist bromocriptine
Transphenoidal surgery or radiation	Large pituitary adenomas
Octrotide p.650	Hormone-secreting tumors:(因somatostatin可-(-)→各種secretion cell的分泌) Acromegaly The carcinoid syndrome Gastrinoma Glucagonoma …etc.
Gonadotropin 女和男不孕症主流藥 ?隱睪症 平時 FSH+LH 排卵時 給大量LH	Ovulation induction p.651 FSH→hCG→progesterone
	Male infertility p.652
Native GnRH	Gonadorelin: acetate of synthetic hGnRH
GnRH analogue	goserelin(Zoladex) Histrelin Leuprolide(Lupron) Nafarelin Triptorelin
GnRH ? 一次大量給 作用劑 持續緩慢給 阻斷	stimulation	Female infertility gonadorelin p.653
		male infertility gonadorelin p.654
		Diagonosis of LH responsiveness p.654
	supression	Controlled ovarian hyperstimulation p.654 Leuprolide (SC) (Lupron) Nafarelin (nasal)
		Endometriosis子宮內膜異位 p.654 Leuprolide(Lupron) Goserelin(Zoladex) Nafarelin
		Uterine leiomyomata肌瘤 p.654 (Uterine fibroids) Leuprolide(Lupron) Goserelin(Zoladex) Nafarelin
		Prostate cancer p.654 Leuprolide(Lupron) Goserelin(Zoladex) Histrelin Coadministrate bicalutamide to avoid tumor flares Triptorelin
		Central precocious puberty p.654 Leuprolide(Lupron) Nafarelin
		Advanced breast and ovarian cancer
		Thining of the endometrial lining in preparation for an endometrial ablation procedure in woman with dysfunctional uterine bleeding.
		Amenorrhea and infertility in women with polycystic ovary disease
GnRH antagonist Ganirelix Cetrorelix Abarelix degarelix	Suppression of gonadotropin production p.655 Ganirelix Cetrorelix
	Advanced prostate cancer p.655 Abarelix degarelix
Menotropin hMG (human menopausal gonadotropin)	Extract of postmenopausal women urine contain substance with LH FSH Property
FSH	Urofollitropin, uFSH: FSH extract of postmenopausal women urine
	rFSH(recombinant FSH) Follitropin α Follitropin β Follitropin α AA sequence is identical to FSH, differ in carbohydrate side chain, shorter t1/2, equel or more potent, more expensive Follitropin β
LH	Lutropin α: used in combination with follitropin α for stimulation of follicular development in infertile women with profound LH deficiency.
	hCG(IM): produced by human placenta and excreted into the urine.
	rhCG(SC)(choriogonadotropin α): the only gonadotropin preparation dosing based on weight but unit of activity.
D2 agonist S1. Ergot alkaloids Bromocriptine Cabergoline S2. Nonergot Ropinirole (Parkinson) Pramipexole (Parkinson) Quinagoline	Hyperprolactinemia Acromegaly(1/3)
Oxytocin
Oxytocin antagonist: atosiban	Preterm labor難產
Vasopressin Desmopressin (DDAVP, 1-desamino-8-D-arginine vasopressin)	Pituitary diabetes insipidus(尿崩症)
Desmopressin (DDAVP, 1-desamino-8-D-arginine vasopressin)	Nocturnal enuresis夜尿 Hemophilia A and von Willebrand’s disease (factor VIII)
Vasopressin	V1 agonist: vasopressor V2 agonist: reduce diuresis→acute CHF Hyponatremia(因其為借水而非Na的?)
Desmopressin (DDAVP, 1-desamino-8-D-arginine vasopressin)	Select V2 agonist: reduce diuresis, Nocturnal enuresis夜尿, Hemophilia A and von Willebrand’s disease (factor VIII) Long-acting
Vasopressin antagonist: Conivaptan Tolvaptan	Conivaptan: ,  antagonist: hyponatremia(IV) Tolvaptan:  antagonist