scholarly journals Developmental changes in localization of steroid synthesis enzymes in camelid placenta

Reproduction ◽  
2003 ◽  
pp. 239-247 ◽  
Author(s):  
FB Wooding ◽  
M Ozturk ◽  
JA Skidmore ◽  
WR Allen
Keyword(s):  
Endoplasmic Reticulum ◽  
Light Microscope ◽  
Smooth Endoplasmic Reticulum ◽  
Giant Cells ◽  
Developmental Changes ◽  
Side Chain ◽  
Steroid Synthesis ◽  
Similar Frequency ◽  
Chain Cleavage ◽  
Multinucleate Giant Cells

The uninucleate trophoblast of epitheliochorial camelid placenta produces multinucleate giant cells starting between day 30 and day 35 of pregnancy. The giant cells are found scattered along the trophoblast at similar frequency throughout gestation. Light microscope immunocytochemistry indicates that the four steroid synthesis enzymes (cholesterol side chain cleavage, 3beta-hydroxysteroid de-hydrogenase, 17alpha-hydroxylase and aromatase) are present in all uninucleate trophoblast cells between day 14 and day 30 of pregnancy, but are found only in the giant cells once they are established, and that this localization persists until term. The giant cells show massive amounts of smooth endoplasmic reticulum and numerous small mitochondria, again as has been shown in other steroid-producing cells. As progesterone from the corpus luteum is necessary throughout gestation in camels, the capacity for oestrogen production by the trophoblast presumably has an important role, but one limited mostly to the immediate vicinity of the fetomaternal interface.

THE ULTRASTRUCTURE OF THE HUMAN GRANULOSAL LUTEIN CELL OF THE FIRST TRIMESTER OF GESTATION

1968 ◽  
Vol 58 (3) ◽  
pp. 481-496 ◽  
Author(s):  
Poul Hjortkjær Pedersen ◽  
Jørgen Falck Larsen
Keyword(s):  
Endoplasmic Reticulum ◽  
Smooth Endoplasmic Reticulum ◽  
First Trimester ◽  
Corpora Lutea ◽  
Steroid Synthesis ◽  
Intracellular Location ◽  
Human Pregnancy ◽  
Subendothelial Space ◽  
Lutein Cell ◽  
Early Human

ABSTRACT The ultrastructure of granulosal lutein cells of 13 corpora lutea in early human pregnancy was studied. The predominant cytoplasmic element was the smooth endoplasmic reticulum. No convincing signs of degeneration of the lutein cells could be demonstrated within the first 14 weeks of pregnancy, as the mitochondria as well as the rough and smooth endoplasmic reticulum were well preserved. However, lysosomes may be slightly more numerous in older specimens and the subendothelial space increases with the age of gestation. A particular type of multilaminated structure one to five micron in diameter was observed, particularly in the earliest specimens. The possible intracellular location of steroid synthesis is discussed.

scholarly journals Androgen profiles during pubertal Leydig cell development in mice

Reproduction ◽  
2010 ◽  
Vol 140 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Xiufeng Wu ◽  
Ramamani Arumugam ◽  
Ningning Zhang ◽  
Mary M Lee
Keyword(s):  
Leydig Cell ◽  
Developmental Changes ◽  
Side Chain ◽  
Adult Rat ◽  
Testosterone Production ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Species Specific

Postnatal Leydig cell (LC) development in mice has been assumed empirically to resemble that of rats, which have characteristic hormonal profiles at well-defined maturational stages. To characterize the changes in LC function and gene expression in mice, we examined reproductive hormone expression from birth to 180 days, and quantified in vivo and in vitro production of androgens during sexual maturation. Although the overall plasma androgen and LH profiles from birth through puberty were comparable to that of rats, the timing of developmental changes in androgen production and steroidogenic capacity of isolated LCs differed. In mice, onset of androgen biosynthetic capacity, distinguished by an acute rise in androstenedione and testosterone production and an increased expression of the steroidogenic enzymes, cytochrome P450 cholesterol side-chain cleavage enzyme and 17α-hydroxylase, occurred at day 24 (d24) rather than at d21 as reported in rats. Moreover, in contrast to persistently high testosterone production by pubertal and adult rat LCs, testosterone production was maximal at d45 in mice, and then declined in mature LCs. The murine LCs also respond more robustly to LH stimulation, with a greater increment in LH-stimulated testosterone production. Collectively, these data suggest that the mouse LC lineage has a delayed onset, and that it has an accelerated pace of maturation compared with the rat LC lineage. Across comparable maturational stages, LCs exhibit species-specific developmental changes in enzyme expression and capacity for androgen production. Our results demonstrate distinct differences in LC differentiation between mice and rats, and provide informative data for assessing reproductive phenotypes of recombinant mouse models.

scholarly journals An Outer Mitochondrial Translocase, Tom22, Is Crucial for Inner Mitochondrial Steroidogenic Regulation in Adrenal and Gonadal Tissues

2016 ◽  
Vol 36 (6) ◽  
pp. 1032-1047 ◽  
Author(s):  
Maheshinie Rajapaksha ◽  
Jasmeet Kaur ◽  
Manoj Prasad ◽  
Kevin J. Pawlak ◽  
Brendan Marshall ◽  
...  
Keyword(s):  
Side Chain ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Enzyme ◽  
Steroid Synthesis ◽  
Cytochrome P450scc ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Terminal Amino ◽  
Interfering Rna ◽  
Amino Acid Segment

After cholesterol is transported into the mitochondria of steroidogenic tissues, the first steroid, pregnenolone, is synthesized in adrenal and gonadal tissues to initiate steroid synthesis by catalyzing the conversion of pregnenolone to progesterone, which is mediated by the inner mitochondrial enzyme 3β-hydroxysteroid dehydrogenase 2 (3βHSD2). We report that the mitochondrial translocase Tom22 is essential for metabolic conversion, as its knockdown by small interfering RNA (siRNA) completely ablated progesterone conversion in both steroidogenic mouse Leydig MA-10 and human adrenal NCI cells. Tom22 forms a 500-kDa complex with mitochondrial proteins associated with 3βHSD2. Although the absence of Tom22 did not inhibit mitochondrial import of cytochrome P450scc (cytochrome P450 side chain cleavage enzyme) and aldosterone synthase, it did inhibit 3βHSD2 expression. Electron microscopy showed that Tom22 is localized at the outer mitochondrial membrane (OMM), while 3βHSD2 is localized at the inner mitochondrial space (IMS), where it interacts through a specific region with Tom22 with its C-terminal amino acids and a small amino acid segment of Tom22 exposed to the IMS. Therefore, Tom22 is a critical regulator of steroidogenesis, and thus, it is essential for mammalian survival.

scholarly journals A role for calmodulin in the regulation of steroidogenesis

1981 ◽  
Vol 90 (2) ◽  
pp. 402-407 ◽  
Author(s):  
PF Hall ◽  
S Osawa ◽  
CL Thomasson
Keyword(s):  
Cyclic Amp ◽  
Adrenal Tumor ◽  
Side Chain ◽  
Dibutyryl Cyclic Amp ◽  
Steroid Production ◽  
Steroid Synthesis ◽  
Side Chain Cleavage ◽  
Cleavage Activity ◽  
Chain Cleavage

Two approaches were used to study the possible role of calmodulin in the regulation of steroid synthesis by mouse adrenal tumor cells: trifluoperazine was used as an inhibitor of calmodulin and liposomes were used to deliver calmodulin into the cells. Trifluoperazine inhibits three steroidogenic responses to both ACTH and dibutyryl cyclic AMP: (a) increase in steroid production, (b) increased transport of cholesterol to mitochondria, and (c) increased side-chain cleavage by mitochondria isolated from cells incubated with ACTH or dibutyryl cyclic AMP. When calmodulin is introduced into the cells via liposomes, steroid synthesis is slightly stimulated. When calmodulin extensively dialyzed against EGTA, this stimulation is abolished. Ca(2+) introduced via liposomes was also without effect. However, when both calmodulin and Ca(2+) are introduced via liposomes (either in separate liposomes or in the same liposomes), steroid synthesis is stimulated. This stimulation does not occur when either anticalmodulin antibodies or EGTA is also present in the liposomes or when trifluoperazine is present in the incubation medium. Calmodulin and Ca(2+) presented together in liposomes to the cells stimulate transport of cholesterol to mitochondria, and side-chain cleavage activity is greater in mitochondria isolated from cells previously fused with liposomes containing calmodulin and Ca(2+) than in mitochondria from cells fused with liposomes containing buffer only. These observations suggest that calmodulin may be involved in regulating the transport of cholesterol to mitochondria, a process which is stimulated by ACTH and dibutyryl cyclic AMP and which may account, at least in part, for the increase in steroid synthesis produced by these agents.

scholarly journals Homozygous Disruption of P450 Side-Chain Cleavage (CYP11A1) Is Associated with Prematurity, Complete 46,XY Sex Reversal, and Severe Adrenal Failure

2005 ◽  
Vol 90 (1) ◽  
pp. 538-541 ◽  
Author(s):  
Olaf Hiort ◽  
Paul-Martin Holterhus ◽  
Ralf Werner ◽  
Christine Marschke ◽  
Ute Hoppe ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Laboratory Data ◽  
Sex Reversal ◽  
Molecular Genetic Analysis ◽  
Side Chain ◽  
Steroid Synthesis ◽  
Cytochrome P450scc ◽  
Side Chain Cleavage ◽  
Fetal Survival ◽  
Chain Cleavage

Abstract Disruption of the P450 side-chain cleavage cytochrome (P450scc) enzyme due to deleterious mutations of the CYP11A1 gene is thought to be incompatible with fetal survival because of impaired progesterone production by the fetoplacental unit. We present a 46,XY patient with a homozygous disruption of CYP11A1. The child was born prematurely with complete sex reversal and severe adrenal insufficiency. Laboratory data showed diminished or absent steroidogenesis in all pathways. Molecular genetic analysis of the CYP11A1 gene revealed a homozygous single nucleotide deletion leading to a premature termination at codon position 288. This mutation will delete highly conserved regions of the P450scc enzyme and thus is predicted to lead to a nonfunctional protein. Both healthy parents were heterozygous for this mutation. Our report demonstrates that severe disruption of P450scc can be compatible with survival in rare instances. Furthermore, defects in this enzyme are inherited in an autosomal-recessive fashion, and heterozygote carriers can be healthy and fertile. The possibility of P450scc-independent pathways of steroid synthesis in addition to the current concept of luteoplacental shift of progesterone synthesis in humans has to be questioned.

scholarly journals Inner Mitochondrial Translocase Tim50 Is Central in Adrenal and Testicular Steroid Synthesis

2018 ◽  
Vol 39 (1) ◽  
Author(s):  
Himangshu S. Bose ◽  
Fadi Gebrail ◽  
Brendan Marshall ◽  
Elizabeth W. Perry ◽  
Randy M. Whittal
Keyword(s):  
Metabolic Activity ◽  
Side Chain ◽  
Protein Amino Acid ◽  
Steroid Synthesis ◽  
Essential Requirement ◽  
Chain Cleavage ◽  
C Terminus ◽  
The Matrix ◽  
Cleavage Enzyme ◽  
First Time

ABSTRACT Adrenal and gonadal mitochondrial metabolic activity requires electrons from cofactors, cholesterol, and a substrate for rapid steroid synthesis, an essential requirement for mammalian survival. Substrate activity depends on its environment, which is regulated by chaperones and mitochondrial translocases. Cytochrome P450 side-chain cleavage enzyme (SCC or CYP11A1) catalyzes cholesterol to pregnenolone conversion, although its mechanism of action is not well understood. We find that SCC is directly imported into the mitochondrial matrix, where its N-terminal sequence is cleaved sequentially, after which it becomes activated following the second cleavage, which is dependent on the folding of the protein. Following integration of the SCC C terminus into the TIM23 complex, amino acids 141 to 146 interact with the intermembrane-exposed Tim50 protein, forming a large complex. The absence of Tim50 or its mutation reduced enzymatic activity. For the first time, we report that a protein activated at the matrix remains mostly unfolded and is transported back to the IMS to integrate with the TIM23 translocase complex and align with the Tim50 protein. Amino acid changes that suppress the association of Tim50 with SCC ablate metabolic activity. Thus, the TIM23 complex is the central regulator of metabolism guided by Tim50.

scholarly journals Cholesterol and Steroid Synthesizing Smooth Endoplasmic Reticulum of Adrenocortical Cells Contains High Levels of Proteins Associated with the Translocation Channel

Endocrinology ◽  
2005 ◽  
Vol 146 (10) ◽  
pp. 4234-4249 ◽  
Author(s):  
Virginia H. Black ◽  
Archana Sanjay ◽  
Klaus van Leyen ◽  
Brett Lauring ◽  
Gert Kreibich
Keyword(s):  
Endoplasmic Reticulum ◽  
Rough Endoplasmic Reticulum ◽  
Smooth Endoplasmic Reticulum ◽  
Steroid Metabolism ◽  
Adrenocortical Cells ◽  
Steroid Synthesis ◽  
Local Synthesis ◽  
Peptide Cleavage ◽  
Cotranslational Translocation ◽  
Tubular Endoplasmic Reticulum

Steroid-secreting cells are characterized by abundant smooth endoplasmic reticulum whose membranes contain many enzymes involved in sterol and steroid synthesis. Yet they have relatively little morphologically identifiable rough endoplasmic reticulum, presumably required for synthesis and maintenance of the smooth membranes. In this study, we demonstrate that adrenal smooth microsomal subfractions enriched in smooth endoplasmic reticulum membranes contain high levels of translocation apparatus and oligosaccharyltransferase complex proteins, previously thought confined to rough endoplasmic reticulum. We further demonstrate that these smooth microsomal subfractions are capable of effecting cotranslational translocation, signal peptide cleavage, and N-glycosylation of newly synthesized polypeptides. This shifts the paradigm for distinction between smooth and rough endoplasmic reticulum. Confocal microscopy revealed the proteins to be distributed throughout the abundant tubular endoplasmic reticulum in these cells, which is predominantly smooth surfaced. We hypothesize that the broadly distributed translocon and oligosaccharyltransferase proteins participate in local synthesis and/or quality control of membrane proteins involved in cholesterol and steroid metabolism in a sterol-dependent and hormonally regulated manner.

In Vitro Induction of Crystals of MT Protein by Vinblastine-Colcemid in Mouse Spermatids

1974 ◽  
Vol 32 ◽  
pp. 132-133
Author(s):  
John J. Wolosewick ◽  
John H. D. Bryan
Keyword(s):  
Endoplasmic Reticulum ◽  
Smooth Endoplasmic Reticulum ◽  
Nuclear Ring ◽  
Rough Er ◽  
Distal Direction ◽  
In Vitro Induction

Early in spermiogenesis the manchette is rapidly assembled in a distal direction from the nuclear-ring-densities. The association of vesicles of smooth endoplasmic reticulum (SER) and the manchette microtubules (MTS) has been reported. In the mouse, osmophilic densities at the distal ends of the manchette are the organizing centers (MTOCS), and are associated with the SER. Rapid MT assembly and the lack of rough ER suggests that there is an existing pool of MT protein. Colcemid potentiates the reaction of vinblastine with tubulin and was used in this investigation to detect this protein.

Hepatic Ultrastructure Changes Induced by Lithocholic Acid

1967 ◽  
Vol 25 ◽  
pp. 162-163 ◽  
Author(s):  
F. G. Zaki
Keyword(s):  
Endoplasmic Reticulum ◽  
Lithocholic Acid ◽  
Smooth Endoplasmic Reticulum ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Electron Microscopic ◽  
Hydropic Degeneration ◽  
Hepatic Cells ◽  
Low Protein ◽  
Microscopic Studies

Addition of lithocholic acid (LCA), a naturally occurring bile acid in mammals, to a low protein diet fed to rats induced marked inflammatory reaction in the hepatic cells followed by hydropic degeneration and ductular cell proliferation. These changes were accompanied by dilatation and hyperplasia of the common bile duct and formation of “gallstones”. All these changes were reversible when LCA was withdrawn from the low protein diet except for the hardened gallstones which persisted.Electron microscopic studies revealed marked alterations in the hepatic cells. Early changes included disorganization, fragmentation of the rough endoplasmic reticulum and detachment of its ribosomes. Free ribosomes, either singly or arranged in small clusters were frequently seen in most of the hepatic cells. Vesiculation of the smooth endoplasmic reticulum was often encountered as early as one week after the administration of LCA (Fig. 1).

Ultrastructural Changes of Smoooth Endoplasmic Reticulum in the Retinal Pigment Epithelium by Choline Chloride

1972 ◽  
Vol 30 ◽  
pp. 58-59
Author(s):  
Kazushige Hirosawa ◽  
Eichi Yamada
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cell ◽  
Smooth Endoplasmic Reticulum ◽  
Pigment Epithelium ◽  
Choline Chloride ◽  
Retinal Pigment ◽  
Ultrastructural Changes ◽  
Lower Vertebrate ◽  
Visual Cells ◽  
Pigment Epithelial

The pigment epithelium is located between the choriocapillary and the visual cells. The pigment epithelial cell is characterized by a large amount of the smooth endoplasmic reticulum (SER) in its cytoplasm. In addition, the pigment epithelial cell of some lower vertebrate has myeloid body as a specialized form of the SER. Generally, SER is supposed to work in the lipid metabolism. However, the functions of abundant SER and myeloid body in the pigment epithelial cell are still in question. This paper reports an attempt, to depict the functions of these organelles in the frog retina by administering one of phospholipid precursors.

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