Hormonal Regulation, Tissue Distribution, and Content of Aromatase Cytochrome P450 Messenger Ribonucleic Acid and Enzyme in Rat Ovarian Follicles and Corpora Lutea: Relationship to Estradiol Biosynthesis*

Hickey, Gerard J.; Chen, Shiuan; Besman, Marc J.; Shively, John E.; Hall, Peter F.; Gaddy-Kurten, Dana; Richards, Joann E S.

doi:10.1210/endo-122-4-1426

Cited by 189 publications

(77 citation statements)

References 40 publications

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“…Luteal cell function is greatly affected by locally produced estradiol, which stimulates both progesterone biosynthesis and luteal cell hypertrophy [67]. As shown in figure 3, luteal aromatase mRNA content is low on day 4 of pregnancy, increases progressively to reach high levels of expression between days 14 and 19, and decreases from day 20 to reach undetectable levels on day 23, the day of parturition [68][69][70]. To facilitate the description of the mechanisms that may control luteal aromatase expression, three periods will be considered: i) luteinization, ii) pregnancy, and iii) before parturition.…”

Section: Pregnant Ratsmentioning

confidence: 99%

Aromatase expression in the ovary: Hormonal and molecular regulation

2008

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Summary-Estrogens are synthesized by the aromatase enzyme encoded by the Cyp19a1 gene, which contains an unusually large regulatory region. In most mammals, aromatase expression is under the control of two distinct promoters a gonad-and a brain-specific promoter. In humans, this gene contains 10 tissue-specific promoters that are alternatively used in various cell types and tumors. Each promoter is regulated by a distinct set of regulatory sequences and transcription factors that bind to these specific sequences. The cAMP/PKA/CREB pathway is considered to be the primary signaling cascade through which the gonad Cyp19 promoter is regulated. Very interestingly, in rat luteal cells, the proximal promoter is not controlled in a cAMP dependent manner. Strikingly, these cells express aromatase at high levels similar to those found in preovulatory follicles, suggesting that alternative and powerful mechanisms control aromatase expression in luteal cells and that the rat corpus luteum represents an important paradigm for understanding alternative controls of the aromatase gene. Here, the molecular and cellular mechanisms controlling the expression of the aromatase gene in granulosa and luteal cells are discussed.

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Section: Pregnant Ratsmentioning

confidence: 99%

Aromatase expression in the ovary: Hormonal and molecular regulation

2008

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“…Under the influence of LH action, theca cells produce androgens, which thereafter are aromatized to estrogens in granulosa Page 4 of 24 A c c e p t e d M a n u s c r i p t cells. Both gonadotropins stimulate the expression of cytochrome P450-aromatase (P450-arom), which is needed for the aromatization of androgens to estrogens in granulosa cells (Hickey et al, 1988). Furthermore, FSH stimulus increases the expression of LHR and other genes in the granulosa cells of preovulatory follicles (Richards, 1994).…”

Section: Classical Gonadal Actions Of Gonadotropinsmentioning

confidence: 99%

Extragonadal LH/hCG action—Not yet time to rewrite textbooks

Pakarainen¹,

Ahtiainen²,

Zhang³

et al. 2007

Molecular and Cellular Endocrinology

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Please cite this article as: Pakarainen, T., Ahtiainen, P., Zhang, F.-P., Rulli, S., Poutanen, M., Huhtaniemi, I., Extragonadal LH/hCG action -not yet time to rewrite textbooks, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t AbstractGonadotropins are indispensable in both sexes in the regulation of gonadal sex steroid production and gametogenesis. In addition to their well established classical actions, numerous recent publications have indicated the presence and function of luteinizing hormone/chorionic gonadotropin receptors (LH/hCG-R) in a variety of extragonadal tissues. However, the physiological significance of such effects has remained unclear. We have generated two genetically modified mouse models, one with excessive production of hCG and the other with targeted disruption of LH/hCG-R gene, and used them to address the functions of LH and hCG.Numerous gonadal and extragonadal phenotypes were found in the models with the two extremes of LH/hCG action. However, when the extragonadal effects were scrutinized in greater detail, they all appeared to arise through modification of gonadal function, either through enhanced or inhibited response to LH/hCG stimulation. Hence, further evidence is needed before the extragonadal LH/hCG-R expression can be considered functionally significant.

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“…The transient, cAMP-mediated induction of several members of the AP1 family that precedes the aromatase expression may contribute to the delayed expression of aromatase, which could serve to ensure a controlled and coordinated hormone biosynthesis. In addition, the mRNA level of aromatase undergoes rapid and dramatic reduction following the LH surge at later stages of folliculogenesis (Hickey et al, 1988;Fitzpatrick and Richards, 1991;Richards, 1994). Interestingly, levels of multiple AP1 proteins including JunD and Fra2 were elevated and remained high when proliferating granulosa cells turned into terminally differentiated, nondividing cells (Sharma and Richards, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Upon the ovarian LH surge, granulosa cells undergo the transition from a proliferating to terminally differentiated state, ultimately becoming luteal cells. This LH-induced transition is accompanied by a rapid reduction in the expression of PO-specific genes including aromatase, as well as induction of gene expression required for ovulation and luteinization (Hickey et al, 1988;Fitzpatrick and Richards, 1991).…”

Section: Introductionmentioning

confidence: 99%

“…Lastly, many FSH-stimulated genes (e.g. aromatase) in granulosa cells are downregulated in response to the LH surge during the early stages of luteinization (Fitzpatrick and Richards, 1991;Hickey et al, 1988). While the positive transcription factors that mediate FSH-stimulated transcription of the aromatase gene have been extensively studied, the molecular basis for the attenuation of the aromatase expression is less understood.…”

Section: Introductionmentioning

confidence: 99%

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