Biomaterial Database

Insulin-like growth factor I inhibits aromatization induced by follice-stimulating hormone in rat sertoli cell culture. 1996

M S Rappaport, and E P Smith

Division of Endocrinology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.

Sertoli cells in the testis and granulosa cells in the ovary convert androgen to estrogen under the primary control of FSH. Insulin-like growth factor I (IGF-I) markedly augments FSH-stimulated estrogen production in the rat granulosa cell. In this study we examined the regulation of aromatase by FSH and characterized the effects of IGF-I on FSH-induced estrogen production by Sertoli cells cultured from the testes of 16-day-old rats. FSH stimulated aromatization of androstenedione in Sertoli cell culture and achieved maximal effectiveness by 12 h of treatment. Analysis of aromatase mRNA by reverse transcription-polymerase chain reaction indicated a marked induction by FSH within 3 h of treatment that was dependent on FSH concentration. IGF-I inhibited FSH-stimulated aromatization dose-dependently; inhibition was approximately 50% by 6 h of cotreatment (p < 0.01). IGF-I was ineffective if added more than 3 h after addition of FSH. Aromatase mRNA was reduced by IGF-I (37 +/- 12%, p < 0.01), coincident with the decrease in estrogen production. To further address the mechanism of IGF-I inhibition, potential interactions with the cAMP and protein kinase C (PKC) signaling pathways were examined. IGF-I inhibited aromatase activity induced by dibutyryl cAMP and inhibited FSH-stimulated estrogen production in the presence of 3-isobutyl-1-methylxanthine, suggesting that IGF-I action was independent of cAMP production. Phorbol-12-myristate-13-acetate (PMA) and IGF-I were additive in their inhibition of FSH. However, down-regulation of PKC prevented PMA inhibition of FSH but not inhibition by IGF-I. We conclude that IGF-I specifically inhibits FSH-induced aromatization in the Sertoli cell in marked contrast to the effects of IGF-I on rat granulosa cells. Although IGF-I and PMA both inhibit aromatase induction, the independence of the IGF-I effect from PKC down-regulation suggests that the initial action of IGF-I is independent of PKC. As IGF-I treatment similarly alters FSH stimulation of both estrogen production and aromatase mRNA, it is likely that the effect of IGF-I on estrogen production in the Sertoli cell is a result, at least in part, of a decrease in aromatase mRNA.

UI	MeSH Term	Description	Entries
D007334	Insulin-Like Growth Factor I	A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.	IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D008297	Male		Males
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004967	Estrogens	Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.	Estrogen,Estrogen Effect,Estrogen Effects,Estrogen Receptor Agonists,Estrogenic Agents,Estrogenic Compounds,Estrogenic Effect,Estrogenic Effects,Agents, Estrogenic,Agonists, Estrogen Receptor,Compounds, Estrogenic,Effects, Estrogen,Effects, Estrogenic,Receptor Agonists, Estrogen
D005640	Follicle Stimulating Hormone	A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.	FSH (Follicle Stimulating Hormone),Follicle-Stimulating Hormone,Follitropin
D000242	Cyclic AMP	An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.	Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001141	Aromatase	An enzyme that catalyzes the desaturation (aromatization) of the ring A of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the CYP19 gene, and functions in complex with NADPH-FERRIHEMOPROTEIN REDUCTASE in the cytochrome P-450 system.	CYP19,Cytochrome P-450 CYP19,Cytochrome P-450(AROM),Androstenedione Aromatase,CYP 19,CYP19 Protein,Cytochrome P450 19,Estrogen Synthase,Estrogen Synthetase,P450AROM,Aromatase, Androstenedione,Cytochrome P 450 CYP19,Protein, CYP19