Involvement of cyclic AMP in the functions of granulosa and luteal cells: regulation of steroidogenesis. 1988

J F Strauss, and T G Golos, and S L Silavin, and E A Soto, and K Takagi
Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia 19104.

The findings reviewed above demonstrate that cAMP can act at several distinct loci to enhance steroidogenesis. Analogs of cAMP stimulate the accumulation of the mRNAs which encode components of the steroidogenic machinery, such as the receptor for LDL and the system for the cleavage of the cholesterol sidechain. This apparently coordinated accumulation of specific mRNAs results from increased transcription of the relevant genes. Transacting factors modulated by cyclic AMP may influence common enhancer sequences (e.g., TGACGTCA), and such interactions would account for the simultaneous increase in expression of specific genes on several different chromosomes. These actions of cyclic AMP enable ovarian cells to support long-term increases in steroid synthesis by increasing the quantities of proteins involved in steroidogenesis. Such changes would obviously be important during luteinization, when the potential of granulosa cells to secrete progesterone is greatly increased. Although we speak of these effects as "long-term", it is evident that they occur within a relatively short time (hours) after exposure of cells to the tropic agent. Cyclic AMP also acts to stimulate steroidogenesis post-transcriptionally. It may influence events at the translational level via interactions in the formation of "labile" proteins. In addition, the regulation of cholesteryl ester hydrolase, as well as of other enzymes involved the metabolism of cholesterol, seems to involve post-translational modifications (e.g., phosphorylation). The effects of cAMP on the cytoskeleton may be another manifestation of a post-translational response. These actions of cAMP promote acute increases in steroidogenesis (i.e., within minutes). They encompass the transport of cholesterol to the mitochondria and the regulation of access of sterol to the inner mitochondrial membranes. Future research should be directed at elucidating the exact mechanisms which permit cAMP to exert coordinate effects on the genome (Figure 8), as well as its post-transcriptional effects on various proteins and enzymes which play a role in the synthesis of steroid hormones.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D003338 Corpus Luteum The yellow body derived from the ruptured OVARIAN FOLLICLE after OVULATION. The process of corpus luteum formation, LUTEINIZATION, is regulated by LUTEINIZING HORMONE. Corpora Lutea,Lutea, Corpora
D005260 Female Females
D006107 Granulosa Cells Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH). Cell, Granulosa,Cells, Granulosa,Granulosa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D013256 Steroids A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed) Steroid,Catatoxic Steroids,Steroids, Catatoxic

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