The ovarian steroids, 17-beta estradiol (E2) and progesterone (P4), are critical for normal uterine function, establishment and maintenance of pregnancy, and mammary gland development. Furthermore, the local effects that are essential for normal ovarian physiology are dependent on the endocrine, paracrine, and autocrine actions of E2, P4, and androgens. In most mammals (including humans and mice), ovarian steroidogenesis occurs according to the two-cell/two-gonadotropin theory. This theory describes how granulosa and theca cells work together to make the ovarian steroids. Theca cells respond to LH signaling by increasing the expression of enzymes necessary for the conversion of cholesterol to androgens, such as androstenedione (A) and testosterone (T). Granulosa cells respond to FSH signaling by increasing the expression of enzymes necessary for the conversion of theca-derived androgens into estrogens (E2 and estrone).

Organismal Systems; Endocrine system
BRITE hierarchy

PMID:15541573

Havelock JC, Rainey WE, Carr BR

Ovarian granulosa cell lines.

Mol Cell Endocrinol 228:67-78 (2004)
DOI:10.1016/j.mce.2004.04.018

PMID:15831519

Stocco DM, Wang X, Jo Y, Manna PR

Multiple signaling pathways regulating steroidogenesis and steroidogenic acute regulatory protein expression: more complicated than we thought.

Mol Endocrinol 19:2647-59 (2005)
DOI:10.1210/me.2004-0532

PMID:20937107

Wen X, Li D, Tozer AJ, Docherty SM, Iles RK

Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles.

Reprod Biol Endocrinol 8:117 (2010)
DOI:10.1186/1477-7827-8-117

PMID:11704115

Erickson GF, Shimasaki S

The physiology of folliculogenesis: the role of novel growth factors.

Fertil Steril 76:943-9 (2001)
DOI:10.1016/S0015-0282(01)02859-X

PMID:11883103

Wood JR, Strauss JF 3rd

Multiple signal transduction pathways regulate ovarian steroidogenesis.

Rev Endocr Metab Disord 3:33-46 (2002)
DOI:10.1023/A:1012748718150

PMID:16603089

Drummond AE

The role of steroids in follicular growth.

Reprod Biol Endocrinol 4:16 (2006)
DOI:10.1186/1477-7827-4-16

PMID:21862696

Craig ZR, Wang W, Flaws JA

Endocrine-disrupting chemicals in ovarian function: effects on steroidogenesis, metabolism and nuclear receptor signaling.

Reproduction 142:633-46 (2011)
DOI:10.1530/REP-11-0136

PMID:20628033

Young JM, McNeilly AS

Theca: the forgotten cell of the ovarian follicle.

Reproduction 140:489-504 (2010)
DOI:10.1530/REP-10-0094

PMID:18440223

Diamanti-Kandarakis E, Argyrakopoulou G, Economou F, Kandaraki E, Koutsilieris M

Defects in insulin signaling pathways in ovarian steroidogenesis and other tissues in polycystic ovary syndrome (PCOS).

J Steroid Biochem Mol Biol 109:242-6 (2008)
DOI:10.1016/j.jsbmb.2008.03.014

PMID:11408113

Spicer LJ

Receptors for insulin-like growth factor-I and tumor necrosis factor-alpha are hormonally regulated in bovine granulosa and thecal cells.

Anim Reprod Sci 67:45-58 (2001)
DOI:10.1016/S0378-4320(01)00114-2

PMID:10630400

Wang X, Stocco DM

Cyclic AMP and arachidonic acid: a tale of two pathways.

Mol Cell Endocrinol 158:7-12 (1999)
DOI:10.1016/S0303-7207(99)00130-6

PMID:17003287

Wang X, Shen CL, Dyson MT, Yin X, Schiffer RB, Grammas P, Stocco DM

The involvement of epoxygenase metabolites of arachidonic acid in cAMP-stimulated steroidogenesis and steroidogenic acute regulatory protein gene expression.

J Endocrinol 190:871-8 (2006)
DOI:10.1677/joe.1.06933

PMID:17008391

Miyoshi T, Otsuka F, Inagaki K, Otani H, Takeda M, Suzuki J, Goto J, Ogura T, Makino H

Differential regulation of steroidogenesis by bone morphogenetic proteins in granulosa cells: involvement of extracellularly regulated kinase signaling and oocyte actions in follicle-stimulating hormone-induced estrogen production.

Endocrinology 148:337-45 (2007)
DOI:10.1210/en.2006-0966

PMID:11447221

Otsuka F, Moore RK, Shimasaki S

Biological function and cellular mechanism of bone morphogenetic protein-6 in the ovary.

J Biol Chem 276:32889-95 (2001)
DOI:10.1074/jbc.M103212200

PMID:14769828

Shimasaki S, Moore RK, Otsuka F, Erickson GF.

The bone morphogenetic protein system in mammalian reproduction.

Endocr Rev 25:72-101 (2004)
DOI:10.1210/er.2003-0007

PMID:16414178

Lukacik P, Kavanagh KL, Oppermann U

Structure and function of human 17beta-hydroxysteroid dehydrogenases.

Mol Cell Endocrinol 248:61-71 (2006)
DOI:10.1016/j.mce.2005.12.007