Mutations in cyclic AMP-dependent protein kinase and corticotropin (ACTH)-sensitive adenylate cyclase affect adrenal steroidogenesis.

Rae, Patricia A.; Gutmann, N S; Tsao, Jennivine; Schimmer, Bernard P.

doi:10.1073/pnas.76.4.1896

Cited by 141 publications

(63 citation statements)

References 47 publications

(45 reference statements)

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“…Moreover, the genetic ablation of vimentin resulted in a 70% decrease in hCG-stimulated progesterone production, compared to wild-type mice, by preovulatory granulosa cells (Shen et al, 2012), although the mice remain fertile (Colucci-Guyon et al, 1994). Trophic hormones, through PKA (Rae et al, 1979), promote mobilization of free cholesterol from intracellular lipid droplets to the outer mitochondrial membrane (Liscum and Munn, 1999) by a series of events that appear to include the disassembly of vimentin filaments (Hall and Almahbobi, 1997;Lee and Mrotek, 1984;Shiver et al, 1992).…”

Section: Disruption Of Vimentin Results In Increased Progesterone Promentioning

confidence: 99%

Dephosphorylation of MAP2D enhances its binding to vimentin in preovulatory ovarian granulosa cells

Flynn

Fiedler

Karlsson

et al. 2016

Journal of Cell Science

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Preovulatory granulosa cells express the low-molecular-mass MAP2D variant of microtubule-associated protein 2 (MAP2). Activation of the luteinizing hormone choriogonadotropin receptor by human choriogonadotropin (hCG) promotes dephosphorylation of MAP2D on Thr256 and Thr259. We sought to evaluate the association of MAP2D with the cytoskeleton, and the effect of hCG on this association. MAP2D partially colocalized, as assessed by confocal immunofluorescence microscopy, with the vimentin intermediate filament and microtubule cytoskeletons in naive cells. In vitro binding studies showed that MAP2D bound directly to vimentin and β-tubulin. Phosphorylation of recombinant MAP2D on Thr256 and Thr259, which mimics the phosphorylation status of MAP2D in naive cells, reduces binding of MAP2D to vimentin and tubulin by two-and three-fold, respectively. PKA-dependent phosphorylation of vimentin (Ser32 and Ser38) promoted binding of vimentin to MAP2D and increased contraction of granulosa cells with reorganization of vimentin filaments and MAP2D from the periphery into a thickened layer surrounding the nucleus and into prominent cellular extensions. Chemical disruption of vimentin filament organization increased progesterone production. Taken together, these results suggest that hCG-stimulated dephosphorylation of MAP2D at Thr256 and Thr259, phosphorylation of vimentin at Ser38 and Ser72, and the resulting enhanced binding of MAP2D to vimentin might contribute to the progesterone synthetic response required for ovulation.

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Section: Disruption Of Vimentin Results In Increased Progesterone Promentioning

confidence: 99%

Dephosphorylation of MAP2D enhances its binding to vimentin in preovulatory ovarian granulosa cells

Flynn

Fiedler

Karlsson

et al. 2016

Journal of Cell Science

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“…Screening of independent recombinants (3ϫ10 5 ) resulted in the isolation of two clones related to p43. The largest clone isolated was 1130 bp with an open reading frame encoding a 311-amino-acid polypeptide followed by a termination codon (TAG) and 197 bp of 3′ untranslated region not including the poly(A) tail.…”

Section: Resultsmentioning

confidence: 99%

An adrenocorticotropin‐regulated phosphoprotein intermediary in steroid synthesis is similar to an acyl‐CoA thioesterase enzyme

Finkielstein

Maloberti

Méndez

et al. 1998

European Journal of Biochemistry

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. (1994) Eur. J. Biochem. 224, 709Ϫ716]. Here, we describe the cloning and sequencing of a cDNA encoding p43 as well as the hormonal regulation of the p43 transcript. The protein resulted homologous to a very recently described mitochondrial peroxisome-proliferator-induced very-long-chain acyl-CoA thioesterase (MTE-I). The deduced amino acid sequence of the protein shows consensus sites for phosphorylation by different protein kinases, and a lipase serine motif. Antibodies raised against a synthetic peptide that includes the lipase serine motif and against the N-terminal region of p43 block the action of the protein. The transcript of p43 was detected in ovary of pseudopregnant rats, rat adrenal zona fasciculata and glomerulosa, mouse Leydig tumor cell line (MA-10), rat brain and human placenta. Inhibition of adrenocorticotropin hormone (ACTH) release and steroid synthesis by dexamethasone produced a dose-dependent decrease in the abundance of the adrenal transcript. The transcript was induced by in vivo stimulation of the adrenals with ACTH. The effect had a rapid onset (5 min), reached maximal stimulation (62%) at 15 min, and returned to basal levels at 30 min. The effect of ACTH on the p43 transcript was inhibited by actinomycin D and enhanced by cycloheximide. Our results provide the first evidence linking acyl-CoA thioesterases with very-long-chain specificities, and a protein intermediary in steroid synthesis, thereby supporting a regulatory role for acyl-CoA thioesterases in steroidogenic tissues.

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“…Y1 adrenocortical tumor cells behave in many respects like normal adrenocortical cells and have long been used as a model adrenocortical cell system (18). Particularly important is the fact that cultures of the Y1 clonal cell line are amenable to genetic approaches such as the classical somatic genetics (19) or the more recent DNA-mediated gene transfer approach (20). Thus, the study of the interaction between ACTH and FGF2 in Y1 adrenocortical cells is timely and methodologically promising.…”

Section: Introductionmentioning

confidence: 99%

Proliferative signaling initiated in ACTH receptors

Lotfi

Lepique

Forti

et al. 2000

Braz J Med Biol Res

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Mutations in cyclic AMP-dependent protein kinase and corticotropin (ACTH)-sensitive adenylate cyclase affect adrenal steroidogenesis.

Cited by 141 publications

References 47 publications

Dephosphorylation of MAP2D enhances its binding to vimentin in preovulatory ovarian granulosa cells

Dephosphorylation of MAP2D enhances its binding to vimentin in preovulatory ovarian granulosa cells

An adrenocorticotropin‐regulated phosphoprotein intermediary in steroid synthesis is similar to an acyl‐CoA thioesterase enzyme

Proliferative signaling initiated in ACTH receptors

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