Sertoli-Leydig cell communications.
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Animals↗
Biomedical subjects
D Naville
Publications and source records attributed to D Naville.
Functional hypersomatotropism in small for gestational age (SGA) newborn infants.
Basal plasma GH levels and the GH responses to an injection of 1 microgram/kg 1-44(NH2) GHRH were determined on day 3 postnatally in 5 small gestational age (SGA) twin newborns and their appropriate gestational age (AGA) co-twins, and in 10 SGA singleton newborns and 6 AGA singleton newborns. The mean basal plasma GH level was higher in the SGA than in the AGA infants but the difference was significant only for singleton newborns (p less than 0.01). The mean peak plasma GH level was markedly increased in SGA compared to AGA infants (p less than 0.05 for twins, p less than 0.01 for singletons). Twelve SGA infants re-tested at 1 month had lower basal and peak plasma GH levels (p less than 0.001 and p less than 0.01). In 21 SGA and 17 AGA infants, serum IGF-I, measured by RIA between 12 and 96 hours after birth, was significantly higher in SGA than in AGA (p less than 0.001). These results suggest that, whatever the mechanism, functional hypersomatotropism is present at day 3 in SGA infants. This hypersomatotropism may participate in the early catch-up growth process.
Gestational Age↗
Differentiating effects of somatomedin-C/insulin-like growth factor I and insulin on Leydig and Sertoli cell functions.
Using an in vitro system of pig Leydig cells (LC) and Sertoli cells (SC) we have demonstrated that: 1) LC contained specific receptors for both somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) and insulin, whereas SC contained only Sm-C/IGF-I receptors; 2) pretreatment of LC with insulin or Sm-C/IGF-I increased hCG receptor number and the cAMP and testosterone responses to this hormone. The enhanced steroidogenic capacity was related to an increased activity of several enzymes of the steroidogenic pathway. At physiological concentrations Sm-C/IGF-I was more potent than insulin, but the effects of the latter peptide at micromolar concentrations were similar to those produced by nanomolar concentrations of Sm-C/IGF-I. However, at maximal concentrations of both peptides, there was no additive effect; 3) the specificity of the effect of Sm-C/IGF-I was proven by the fact that all the effects induced by this peptide, but not by insulin, were blunted by an anti-Sm-C/IGF-I antibody; 4) pretreatment of SC with Sm-C/IGF-I at nM concentrations or with insulin (but only at microM concentrations) enhanced the stimulatory effect of FSH on cAMP production and the secretion of plasminogen activator; 5) in both LH and SC, Sm-C/IGF-I had small mitogenic effects but potentiated the mitogenic action of fibroblast growth factor (FGF). The effect of insulin was observed only at microM concentrations; 6) SC secreted a factor which had physico-chemical and biological properties similar to that of Sm-C/IGF-I. The secretion of this factor was stimulated by FGF and EGF.
Animals↗
Maturation of steroidogenic cells: a target for IGF-I.
Using primary culture of steroidogenic cells in vitro, in serum-free chemically defined medium, strong evidence has been provided for actions of IGF-I on the differentiation of immature Leydig cells and on the maintenance of a differentiated function of mature adrenocortical cells. These data point to the steroidogenic cells as a target for IGF-I action. They also add further evidence for a role of IGF-I in the differentiation process. These actions can be of importance in normal physiological situations as well as in abnormal conditions where IGF-I is decreased, such as hypopituitarism and malnutrition.
Adrenal Cortex↗
Somatomedin-C/insulin-like growth factor 1-like material secreted by porcine Sertoli cells in vitro: characterization and regulation.
Conditioned medium from pig Sertoli cells cultured in a chemically defined medium containing 3H-leucine contains a peptide with properties similar to that of human purified plasma and recombinant DNA somatomedin-C/insulin-like growth factor 1 (Sm-C/IGF-1). Purification of this peptide was achieved by affinity chromatography using mouse monoclonal anti-Sm-C/IGF-1 antibodies and reverse-phase high pressure liquid chromatography on a Bondapak C18 column. Polyacrylamide gel electrophoresis of the purified material gives a single spot after staining or in the autoradiogram, with identical molecular weight to that of pure human Sm-C/IGF-1. The purified peptide behaves like both the pure and recombinant DNA Sm-C/IGF-1 in the specific RIA and/or radioreceptor assays. Under basal conditions the amount of Sm-C/IGF-1 secreted by Sertoli cells was about 4 ng/10(6) cells/24 h, but it decreased during culture. Neither growth hormone nor follitropin were able to stimulate Sm-C/IGF-1 secretion, but both fibroblast growth factor and epidermal growth factor enhanced two- to three-fold its secretion. In addition, cells pretreated for 24 h with these growth factors became sensitive to the stimulatory effect of FSH. Since previous in vitro studies have shown that Sm-C/IGF-1 is a mitogenic and differentiating factor for both Sertoli and Leydig cells, it is possible that Sm-C/IGF-1 secreted by Sertoli cells might play a paracrine and/or autocrine role in the regulation of testicular function.
Animals↗
Somatomedin-C/insulin-like growth factor 1: a differentiating factor of testicular function.
Using primary culture in a chemically defined medium of somatic testicular cells from immature pig, we were able to demonstrate synthesis and secretion of Somatomedin-C/Insulin-Like Growth Factor 1 (Sm-C/IGF-1) by Sertoli cells, a process that is stimulated by Fibroblast Growth Factor (FGF). The presence of IGF type 1 receptor was demonstrated on Sertoli cells. Sm-C/IGF-1 stimulates and potentiates the effects of FGF on both cell multiplication and secretion of plasminogen activator. The presence of both IGF type 1 and insulin receptors was also documented on immature Leydig cells. Pre-incubation of immature Leydig cells for 48 hours with Sm-C/IGF-1 resulted in a dramatic dose-dependent increment of both the LH receptor number and steroidogenic response to LH as well as a clear stimulation of DNA synthesis. These data provide new important insights on the role played by Sm-C, a growth and differentiating factor, on the maturation of the male gonad endocrine function.
Animals↗
Syndrome of congenital adrenocortical unresponsiveness to ACTH. Report of six patients.
Familial glucocorticoid deficiency (FGD) or unresponsiveness to ACTH at the receptor level is a rare autosomal recessive hereditary syndrome characterized by a low cortisol level despite high serum ACTH concentration. Aldosterone levels are normal. The clinical entity generally presents in the first year of life with skin hyperpigmentation and hypoglycemic convulsions. Cortisol response to exogenous ACTH is also absent. Unresponsiveness to ACTH may be due to a mutation in the ACTH receptor; sometimes no mutation is found. We discuss the clinical and laboratory findings and genetic studies in six patients with a diagnosis of FGD. A homozygous V142L mutation was detected in three of the patients and a homozygous D103N mutation was detected in two patients.
Adrenal Cortex↗
SF-1 and the transcriptional regulation of the human ACTH receptor gene.
The adrenocorticotropin receptor or ACTH-R which is the type 2 among the melanocortin receptor family is almost exclusively expressed in the adrenal cortex, reflecting a high degree of tissue specificity. In human cultured adrenocortical cells, we have previously reported that ACTH in contrast to most of the peptide hormones, is able to up-regulate the number of its own receptors through an increase of the transcriptional activity of the encoding gene. Three putative SF-1 binding sites are present in the sequence of the human ACTH-R gene promoter at -35 (SF-35), -98 (SF-98) and -209 (SF-209). By EMSA studies, we demonstrated that these sites effectively bind SF-1 protein. After transient transfection of H295R cells using a construct containing the first 263 bp upstream of the transcriptional start site, in front of the luciferase gene in the pGL3 vector, we demonstrated the involvement of all three SF-1 sites to confer maximal constitutive activity to a proximal region of the hACTH-R gene promoter. Only SF-35 and SF-98 play a role in cAMP-induced regulation of this gene.
Adrenal Cortex↗
Functional activity of 3beta-hydroxysteroid dehydrogenase/isomerase.
3Beta-hydroxysteroid dehydrogenase/steroid delta5-isomerase (3beta-HSD/isomerase) was expressed by baculovirus in Spodoptera fungiperda (Sf9) insect cells from cDNA sequences encoding the human wild-type I (placental) enzyme and the human type I mutant- Y253F. The wild-type and Y253F enzymes were each purified as a single, homogeneous protein from a suspension of the Sf9 cells. Ultraviolet (UV) spectral analyses showed that the wild-type enzyme induced changes in the UV spectrum of the competitive isomerase inhibitor, 19-nortestosterone, and the Y253F mutant did not. The wild-type isomerase required activation by coenzyme to produce the spectral shift. Activation of isomerase by NADH produced a greater change in the 19-nortestosterone spectrum than activation by NAD+. These observations provide direct evidence that Tyr253 functions as the general acid (proton donor) in the isomerase reaction mechanism. Furthermore, the coenzyme-activation profiles support our proposed two-step enzyme mechanism in which NADH produced by the 3beta-HSD activity induces the enzyme to assume the isomerase conformation.
Animals↗