卵巢的一生

The Putative Intraovarian Regulators


......... 前言 .........
    卵巢的follicular growth為何會有週期性? 是什麼因素在決定follicle的atresia? 各follicle所能成長的程度為何不同? 為何某一個follicle會被選為dominant follicle?

除了gonadotropin 及 gonadal steroid是一個決定因素外, 卵巢內部應該另有一些細密的因素來微調這一串很規律的活動. 這些因素因為是具有local production, local reception, 及local action的特色, 所以稱之為"intraovarian regulators". 我們雖然很相信有這些regulators的存在, 但是事實上, 我們對他們的瞭解仍然有限, 將來更深入的研究及發現, 應該可以更合理的解釋更多的現象.

 
  Isulin-like growth factors family  
    簡稱IGFs, 結構及功能很類似insulin, , 屬於low-molecular-weight, single chain polypeptide,IGF-I(70-amino acid)及IGF-II(67-amino acid)是它的兩個主要成員, 最重要的功能是: 加強gonadotropin在卵巢的作用.

IGF-II是最主要的IGFs, 1.在dominant follicle: IGF-II是一種paracrine regulator. 2.在其他antral follicle, IGF-II在theca cell為autocrine, 在granulosa cell則為paracrine.

IGFs另外還可以促成六種IGF-binding proteins(IGFBPs), 顯示IGFs有多個位置的調控作用.

至於IGF-I則有puberty-promoting的作用.

 
  Epidermal growth factor family  
    簡稱EGF, 53-amino acid, sigle chain polypeptide, TGF-a是EGF的analogue, 含50-amino acid

在卵巢, EGF具有強力調節granulosa cell的增生及分化的功能, TGF-a則有抑制granulosa cell分化的功能 .

 
  Trasforming growth factor family  
    簡稱TGF, 屬於25-kDa polypeptide一族, two homodimeric chain, 主要的三個isoform 為TGF-b1, TGF-b2, TGF-b3. 在oocyte, granulosa cell及theca cell 都可測出以上三種isoform.

最重要的是:TGF-b1及TGF-b2能主導granulosa cell 形成inhibinactivin

Ihibin的主要功能在抑制pituitary分泌FSH, inhibin B主要出現在follicular phase, LH-surge 之後就測不到了, inhibin A則出現在follicular phase的後期, 至luteal phase達到高峰.

Activin可以促進pituitary分泌FSH, 在循環血液中activin因為大部分與protein結合(主要是follistatin), 因此並沒有什麼功能, 但是由granulosa cell產生的activin, 抑制theca cell 形成androgen, 抑制granulosa cell形成progesterone及estrogen.

 
  Fibroblast growth factor family  
    簡稱FGF, 146-amino acid polypeptide, 主要在維持corpus luteum上的granulosa-luteal cell的成長.  
  Interleukins  
    簡稱IL-1, polypeptide cytokine, 主要在防止intraovarian luteinization及premature follicular lutenization, 高量的progesterone會抑制IL-1的活動力.  
  Tumor necrosis factor-a  
    簡稱TNF-a, derived from activated resident ovarian "MACROPHAGES", 157-amino acid polypeptide,

主要功能: 1.attenuate the differentiating granulosa cell, 2. for regressing corpora lutea

懷孕或假性懷孕時, 其corpus luteum卻測不出TNF-a

 
  Catecholaminergic input  
    1.Ovarian theca-interstitial cells may be the recipients of direct sympathetic innervation by noradrenergic nerve.

2.Catecholamine also can activate the cAMP transduction sequence in a follicle-closed granulosa cell, resulting in the promotion of progesterone, but not estrogen.

3.Adrenergically supported androgen production may play a role in the regulation of granulosa cell estrogen production, thereby participating in the follicular recruitment and selection.

4.Excessive activation of thecal adrenergic receptors may play a role in the pathogenesis of conditions associated with ovarian hyperandrogenism.

 
  Other Peptides  
   
1. The ovarian renin-angiotensin system
2. corticotropin-releasing factor
3. luteinization inhibitor
4. oocyte maturation inhibitor
5. gonadotropin surge-inhibiting factor
 
       
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