Differentiation of granulosa cell line

Follicle-stimulating hormone induces formation of lamellipodia and filopodia via the adenylyl cyclase/cyclic adenosine monophosphate signal

Nicole A. Grieshaber, Scott A Boitano, Inhae Ji, Jennie P. Mather, Tae H. Ji

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

FSH plays a crucial role in granulosa cell differentiation and follicular development during the ovulation cycle. The early events of granulosa cell differentiation in cell culture involve changes in the cell morphology and cell-to-cell interactions. To determine the cause and signaling mechanism for these changes, we examined an undifferentiated rat ovarian granulosa cell line that grows in a defined serum-free medium, expresses the FSH receptor, terminally differentiates when exposed to FSH, and undergoes apoptosis upon FSH withdrawal. FSH bound the FSH receptor on rat ovarian granulosa cells, and the liganded receptor activated adenylyl cyclase (AC) to produce cAMP but did not mobilize Ca2+. In addition, we observed massive reorganization of the actin cytoskeleton within 3 h of FSH treatment. This involves formation of lamellipodia and filopodia and spreading of multilayer cell aggregates to monolayers. This actin reorganization and cell transformation could also be induced by the AC activator, forskolin, in the absence of FSH. Furthermore, AC inhibitors blocked the FSH-dependent actin reorganization and transformation. On the other hand, phospholipase C inhibitors did not block the FSH-induced changes. Taken together, our observations indicate that the AC/cAMP signal is necessary and sufficient for FSH-dependent granulosa cell differentiation, including massive reorganization of the actin cytoskeleton and changes in the cell morphology and cell-to-cell inter-actions. There is no evidence that the phospholipase C signal and Ca2+ mobilization are involved in this process.

Original languageEnglish (US)
Pages (from-to)3461-3470
Number of pages10
JournalEndocrinology
Volume141
Issue number9
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Pseudopodia
Granulosa Cells
Follicle Stimulating Hormone
Adenylyl Cyclases
Cyclic AMP
Cell Line
FSH Receptors
Cell Differentiation
Type C Phospholipases
Actin Cytoskeleton
Actins
Serum-Free Culture Media
Colforsin
Ovulation
Cell Communication
Cell Culture Techniques
Apoptosis

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Differentiation of granulosa cell line : Follicle-stimulating hormone induces formation of lamellipodia and filopodia via the adenylyl cyclase/cyclic adenosine monophosphate signal. / Grieshaber, Nicole A.; Boitano, Scott A; Ji, Inhae; Mather, Jennie P.; Ji, Tae H.

In: Endocrinology, Vol. 141, No. 9, 2000, p. 3461-3470.

Research output: Contribution to journalArticle

@article{28983e84625d4348a26f04ac5c321250,
title = "Differentiation of granulosa cell line: Follicle-stimulating hormone induces formation of lamellipodia and filopodia via the adenylyl cyclase/cyclic adenosine monophosphate signal",
abstract = "FSH plays a crucial role in granulosa cell differentiation and follicular development during the ovulation cycle. The early events of granulosa cell differentiation in cell culture involve changes in the cell morphology and cell-to-cell interactions. To determine the cause and signaling mechanism for these changes, we examined an undifferentiated rat ovarian granulosa cell line that grows in a defined serum-free medium, expresses the FSH receptor, terminally differentiates when exposed to FSH, and undergoes apoptosis upon FSH withdrawal. FSH bound the FSH receptor on rat ovarian granulosa cells, and the liganded receptor activated adenylyl cyclase (AC) to produce cAMP but did not mobilize Ca2+. In addition, we observed massive reorganization of the actin cytoskeleton within 3 h of FSH treatment. This involves formation of lamellipodia and filopodia and spreading of multilayer cell aggregates to monolayers. This actin reorganization and cell transformation could also be induced by the AC activator, forskolin, in the absence of FSH. Furthermore, AC inhibitors blocked the FSH-dependent actin reorganization and transformation. On the other hand, phospholipase C inhibitors did not block the FSH-induced changes. Taken together, our observations indicate that the AC/cAMP signal is necessary and sufficient for FSH-dependent granulosa cell differentiation, including massive reorganization of the actin cytoskeleton and changes in the cell morphology and cell-to-cell inter-actions. There is no evidence that the phospholipase C signal and Ca2+ mobilization are involved in this process.",
author = "Grieshaber, {Nicole A.} and Boitano, {Scott A} and Inhae Ji and Mather, {Jennie P.} and Ji, {Tae H.}",
year = "2000",
doi = "10.1210/en.141.9.3461",
language = "English (US)",
volume = "141",
pages = "3461--3470",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "9",

}

TY - JOUR

T1 - Differentiation of granulosa cell line

T2 - Follicle-stimulating hormone induces formation of lamellipodia and filopodia via the adenylyl cyclase/cyclic adenosine monophosphate signal

AU - Grieshaber, Nicole A.

AU - Boitano, Scott A

AU - Ji, Inhae

AU - Mather, Jennie P.

AU - Ji, Tae H.

PY - 2000

Y1 - 2000

N2 - FSH plays a crucial role in granulosa cell differentiation and follicular development during the ovulation cycle. The early events of granulosa cell differentiation in cell culture involve changes in the cell morphology and cell-to-cell interactions. To determine the cause and signaling mechanism for these changes, we examined an undifferentiated rat ovarian granulosa cell line that grows in a defined serum-free medium, expresses the FSH receptor, terminally differentiates when exposed to FSH, and undergoes apoptosis upon FSH withdrawal. FSH bound the FSH receptor on rat ovarian granulosa cells, and the liganded receptor activated adenylyl cyclase (AC) to produce cAMP but did not mobilize Ca2+. In addition, we observed massive reorganization of the actin cytoskeleton within 3 h of FSH treatment. This involves formation of lamellipodia and filopodia and spreading of multilayer cell aggregates to monolayers. This actin reorganization and cell transformation could also be induced by the AC activator, forskolin, in the absence of FSH. Furthermore, AC inhibitors blocked the FSH-dependent actin reorganization and transformation. On the other hand, phospholipase C inhibitors did not block the FSH-induced changes. Taken together, our observations indicate that the AC/cAMP signal is necessary and sufficient for FSH-dependent granulosa cell differentiation, including massive reorganization of the actin cytoskeleton and changes in the cell morphology and cell-to-cell inter-actions. There is no evidence that the phospholipase C signal and Ca2+ mobilization are involved in this process.

AB - FSH plays a crucial role in granulosa cell differentiation and follicular development during the ovulation cycle. The early events of granulosa cell differentiation in cell culture involve changes in the cell morphology and cell-to-cell interactions. To determine the cause and signaling mechanism for these changes, we examined an undifferentiated rat ovarian granulosa cell line that grows in a defined serum-free medium, expresses the FSH receptor, terminally differentiates when exposed to FSH, and undergoes apoptosis upon FSH withdrawal. FSH bound the FSH receptor on rat ovarian granulosa cells, and the liganded receptor activated adenylyl cyclase (AC) to produce cAMP but did not mobilize Ca2+. In addition, we observed massive reorganization of the actin cytoskeleton within 3 h of FSH treatment. This involves formation of lamellipodia and filopodia and spreading of multilayer cell aggregates to monolayers. This actin reorganization and cell transformation could also be induced by the AC activator, forskolin, in the absence of FSH. Furthermore, AC inhibitors blocked the FSH-dependent actin reorganization and transformation. On the other hand, phospholipase C inhibitors did not block the FSH-induced changes. Taken together, our observations indicate that the AC/cAMP signal is necessary and sufficient for FSH-dependent granulosa cell differentiation, including massive reorganization of the actin cytoskeleton and changes in the cell morphology and cell-to-cell inter-actions. There is no evidence that the phospholipase C signal and Ca2+ mobilization are involved in this process.

UR - http://www.scopus.com/inward/record.url?scp=0034455591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034455591&partnerID=8YFLogxK

U2 - 10.1210/en.141.9.3461

DO - 10.1210/en.141.9.3461

M3 - Article

VL - 141

SP - 3461

EP - 3470

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 9

ER -