[Human folliculogenesis and local regulation].
It is well known that gonadotropin controls a major part of follicular development. However, the mechanism of local regulation under the control of gonadotropins in still unclear. In this study, we focused on the local regulation of steroidogenesis, growth factors and cell proliferation to evaluate the human follicular development. To assess steroidogenesis, it is important to detect the expression of steroidogenic enzymes in the granulosa and theca cells during folliculogenesis. We initially tried to find out the transcription factor Ad4BP that binds the Ad4 site and regulates the function of steroidogenic enzyme. By immunohistochemistry, the expression of Ad4BP was confirmed sporaf1p4lly in preantral granulosa cells. In the antral follicles, the expression of Ad4BP was observed both in the granulosa and theca cell. According steroidogenic enzyme, we evaluated temporal and spatial localization of cholesterol side chain cleavage (scc), 3 beta hydroxysteroid dehydrogenase (3 beta HSD), 17 alpha hydroxylase (17 alpha) and aromatase, and steroid receptors. In briefly, the localizations of scc, 3 beta HSD and 17 alpha were observed in preantral follicles and the mRNA expressions of these enzymes were confirmed in the theca cell by in situ hybridization method. Expression of aromatase was generally observed in only one follicle (antral or mature follicle) per case in mid proliferative to premenstrual phase. The localization of androgen and estrogen receptor was observed in the antral follicle granulosa cells, and estrogen receptor was detected only in aromatase positive follicles. These results suggested that Ad4BP initially controls the function of steroidogenic enzymes and steroidogenic enzymes gradually express from primary follicles to mature follicles. At antral follicle stage, steroid metabolism completes to produce testosterone. When aromatase and estrogen receptor express in antral follicle, this antral follicle develops as the dominant follicle and produces estradiol to promote follicle maturation. We therefore speculate that the expression of aromatase and estrogen receptor have an important role for the selection of dominant follicle in human. According growth factors for follicular development, it has been demonstrated to be important in the biological activity in the ovary. In this study, we examined the localization of EGF, TGF alpha and their receptor (EGFR). The localization of EGF was not confirmed both mRNA and protein level through follicular development. On the other hand, the localization and expression of TGF alpha was confirmed in theca cells and EGFR in granulosa cells at antral stage.(ABSTRACT TRUNCATED AT 400 WORDS)
Fukaya
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T
Maternal and Perinatal Center, School of Medicine University of Tohoku, Sendai.
D015096:3-Hydroxysteroid Dehydrogenases / Q000502:physiology; D001141:Aromatase / Q000502:physiology; D002455:Cell Division; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006133:Growth Substances / Q000502:physiology; D018398:Homeodomain Proteins; D006801:Humans; D006080:Ovarian Follicle / Q000166:cytology / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid / Q000502:physiology; D013254:Steroid 17-alpha-Hydroxylase / Q000502:physiology; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000502:physiology
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D012739:Gonadal Steroid Hormones; D006133:Growth Substances; D018398:Homeodomain Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D015096:3-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme