Effects of FSH on Leydig cell morphology and function in the hypogonadal mouse

1992 ◽  
Vol 135 (3) ◽  
pp. 517-NP ◽  
Author(s):  
P. J. O'Shaughnessy ◽  
M. K. Bennett ◽  
I. S. Scott ◽  
H. M. Charlton
Keyword(s):  
Leydig Cell ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Cell Function ◽  
Reductase Activity ◽  
Fold Increase ◽  
Paracrine Factors ◽  
Androgen Synthesis ◽  
Congenital Deficiency ◽  
Stimulation Of

ABSTRACT The hypogonadal (hpg) mouse has a congenital deficiency in gonadotrophin-releasing hormone and the gonads consequently lack exposure to endogenous gonadotrophins during development. To determine the effect of FSH on Leydig cell function in these animals adult hpg mice were injected twice daily with FSH (2 μg injections) or LH (40 ng injections, the presumed LH contamination of FSH used). Following FSH treatment there was a clear stimulation of the seminiferous epithelium and in animals injected with FSH plus [3H]thymidine, the incorporation of label was largely confined to the germ cells with no apparent uptake by the Sertoli cells. In FSH-treated testes the Leydig cells contained numerous large lipid droplets, similar to the unstimulated hpg testis. There was no evidence of the interstitial hyperplasia which is observed following injection of high doses of LH (2 pg twice daily). There was no change in basal androgen content of the testis in vivo following FSH treatment but injection of a maximal dose of human chorionic gonadotrophin (hCG), 1 h before death, markedly increased testicular androgen content only in the FSH-treated group. Testicular androgen production in vitro was significantly increased following FSH treatment both under basal conditions (FSH-treated, 17·4 pmol/testis; control, 1·46 pmol/testis) and during stimulation by hCG (FSH-treated, 940 pmol/testis; control, 81 pmol/testis). Associated with the increased androgen production following FSH treatment there were significant increases in the activities of three steroidogenic enzymes; cholesterol side-chain cleavage (186-fold increase over control), 17α-hydroxylase (103-fold increase) and 17-ketosteroid reductase (177-fold increase). The fourth enzyme involved in androgen synthesis, 3β-hydroxysteroid dehydrogenase, shows relatively high activity in the control hpg testis and was only increased by sixfold following FSH treatment. There was no effect of FSH on 5α-reductase activity. Results show that FSH causes a marked stimulation of the steroidogenic capacity of the hpg testis. Leydig cells do not contain FSH receptors and it is assumed that FSH acts through paracrine factors released by the Sertoli cells. Journal of Endocrinology (1992) 135, 517–525

Adult rat Sertoli cells secrete a factor or factors which modulate Leydig cell function

1987 ◽  
Vol 114 (3) ◽  
pp. 459-467 ◽  
Author(s):  
V. Papadopoulos ◽  
P. Kamtchouing ◽  
M. A. Drosdowsky ◽  
M. T. Hochereau de Reviers ◽  
S. Carreau
Keyword(s):  
Cyclic Amp ◽  
Sertoli Cell ◽  
Leydig Cell ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Cell Function ◽  
Cell Interaction ◽  
Adult Rats ◽  
Adult Rat ◽  
Stimulating Factor

ABSTRACT Production of testosterone and oestradiol-17β by Leydig cells from adult rats was stimulated by LH or dibutyryl cyclic AMP (10 and 2·5-fold respectively). The addition of spent medium from normal, hemicastrated or γ-irradiated rat seminiferous tubule cultures, as well as from Sertoli cell cultures, to purified Leydig cells further enhanced both basal (44 and 53% for testosterone and oestradiol-17β respectively) and LH-stimulated (56 and 18%) steroid output. Simultaneously, a decrease (20–30%) in intracellular cyclic AMP levels was observed. This stimulating factor (or factors) secreted by the Sertoli cells is different from LHRH, is of proteinic nature and has a molecular weight ranging between 10 000 and 50 000; its synthesis is not controlled by FSH nor by testosterone. This factor(s) involved in rat Leydig cell steroidogenesis, at a step beyond the adenylate cyclase, does not require protein synthesis for testosterone formation whereas it does for oestradiol-17β production. It should be noted that a germ cell–Sertoli cell interaction modulates the synthesis of this factor(s). J. Endocr. (1987) 114, 459–467

scholarly journals Role of gonadotrophins in regulating numbers of Leydig and Sertoli cells during fetal and postnatal development in mice

Reproduction ◽  
2001 ◽  
pp. 227-234 ◽  
Author(s):  
PJ Baker ◽  
PJ O'Shaughnessy
Keyword(s):  
Cell Volume ◽  
Postnatal Development ◽  
Leydig Cell ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Normal Values ◽  
Fold Increase ◽  
Adult Mice ◽  
Number Of Cells

The role of the gonadotrophins in regulating numbers of Leydig and Sertoli cells during fetal and postnatal development was examined using normal mice and hypogonadal (hpg) mice, which lack circulating gonadotrophins. The disector method was used to determine the number of cells from day 16 of gestation until adulthood. The numbers of Leydig cells did not change significantly between day 16 of gestation and day 5 after parturition in normal mice and were not significantly different from numbers in hpg mice at any age up to day 5 after parturition. There was a 16-fold increase in the number of Leydig cells in normal mice between day 5 and day 20 after parturition, followed by a further doubling of number of cells between day 20 and adulthood. The number of Leydig cells in hpg testes did not change between day 5 and day 20 after parturition but doubled between day 20 and adulthood so that the number of cells was about 10% of normal values from day 20 onwards. Leydig cell volume was constant in normal animals from birth up to day 20 and then showed a 2.5-fold increase in adult animals. Leydig cell volume was normal in hpg testes at birth but decreased thereafter and was about 20% of normal volume in adult mice. The number of Sertoli cells increased continuously from day 16 of gestation to day 20 after gestation in normal mice and then remained static until adulthood. The number of Sertoli cells in hpg testes was normal throughout fetal life but was reduced by about 30% on day 1 (day of parturition). Thereafter, Sertoli cells proliferated at a slower rate but over a longer period in the hpg testis so that on day 20 after parturition the number of Sertoli cells was about 50% of normal values, whereas in adult mice the number was 65% of normal. The number of gonocytes did not change between day 16 of gestation and day 1 and did not differ between normal and hpg testes. The number of gonocytes increased nine-fold in normal testes but only three-fold in hpg testes between day 1 and day 5 after parturition. Gonocytes differentiated into spermatogonia in both normal and hpg testes between day 5 and day 20 after parturition. These results show: (i) that fetal development of both Sertoli and Leydig cells is independent of gonadotrophins; (ii) that normal differentiation and proliferation of the adult Leydig cell population (starting about day 10 after parturition) is dependent on the presence of gonadotrophins; and (iii) that the number of Sertoli cells after birth is regulated by gonadotrophins, although proliferation will continue, at a lower rate and for longer, in the absence of gonadotrophins.

Cultured Sertoli cell-mediated FSH stimulatory effect on Leydig cell steroidogenesis

1985 ◽  
Vol 248 (2) ◽  
pp. E176-E181
Author(s):  
M. Benahmed ◽  
J. Reventos ◽  
E. Tabone ◽  
J. M. Saez
Keyword(s):  
Sertoli Cell ◽  
Leydig Cell ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Cell Function ◽  
Cell Activity ◽  
Defined Medium ◽  
Cell Number ◽  
Two Parameters ◽  
Leydig Cell Function

To determine the precise role of Sertoli cells in the stimulating effects of follicle stimulating hormone (FSH) on Leydig cell activity, porcine purified Leydig and Sertoli cells were cultured separately or together in a chemically defined medium in the absence or presence of porcine, FSH 50 ng/ml. Leydig cell activity was evaluated using two parameters: human chorionic gonadotropin (hCG) binding sites; and hCG-stimulated cAMP production and testosterone secretion. First, it was found that FSH increases Leydig cell activity in crude Leydig cell preparations (40–60% of Leydig cells), whereas it exerts no effect on purified Leydig cells (greater than 90% of Leydig cells). Second, FSH stimulates the activity of Leydig cells cocultured with Sertoli cells, whereas it remains without effect on purified Leydig cells cultured alone. This stimulating effect of FSH on Leydig cell activity is dependent on the Sertoli cell number in the coculture. These data 1) show that the stimulating effect of FSH on Leydig cell function is mediated by Sertoli cells and 2) support the concept of local control of Leydig cell function originating from Sertoli cells.

Effects of hypophysectomy and human chorionic gonadotrophin on Leydig cell function in mature rats

1990 ◽  
Vol 126 (3) ◽  
pp. 367-NP ◽  
Author(s):  
D. M. Stocco ◽  
K. J. Teerds ◽  
M. van Noort ◽  
F. F. G. Rommerts
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Function ◽  
Fold Increase ◽  
Specific Protein ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Cell Functions ◽  
Complete Restoration ◽  
Hypophysectomized Rats

ABSTRACT The biochemical activities involved in the maintenance of Leydig cell functions, and the effects of hypophysectomy and human chorionic gonadotrophin (hCG) on these functions are largely unknown. In the present study, adult hypophysectomized rats were used as a model to determine the effects of these treatments on a number of biochemical and morphological parameters. After 33 days of hypophysectomy, the morphology of the Leydig cells had been drastically altered. In addition, α-naphthol and β-naphthol esterase activity as well as the steroidogenic capacity of the Leydig cells were greatly reduced at this time. In contrast, the level of sterol carrier protein 2 (SCP2), a Leydig cell-specific protein, was affected by hypophysectomy much less than the other parameters measured. Two daily injections of hCG to rats hypophysectomized for 31 days resulted in no change in the morphology of the Leydig cells, or in their proliferative activity. Non-specific esterase activities were also unaffected by 2 days of treatment with hCG. However, two injections of hCG to rats hypophysectomized for 31 days resulted in nearly complete restoration of steroidogenic capacity, and a 3·5-fold increase in the level of SCP2. These findings indicate that hypophysectomy results in significant morphological and biochemical changes in Leydig cells, and that hCG is capable of restoring some of these capacities within a short time. Journal of Endocrinology (1990) 126, 367–375

248. Oestrogen receptor beta is involved in the regulation of Leydig cell number in the mouse

2005 ◽  
Vol 17 (9) ◽  
pp. 99
Author(s):  
M. Gould ◽  
H. D. Nicholson
Keyword(s):  
Leydig Cell ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Oestrogen Receptor ◽  
Physiological Role ◽  
Plasma Testosterone ◽  
Testis Weight ◽  
Wild Type ◽  
Significant Difference ◽  
Receptor Beta

Recent evidence suggests that oestrogen plays a physiological role in the testis. Both oestrogen receptor alpha and oestrogen receptor beta (ERb) are present in the testis and administration of oestrogen has been shown to inhibit the development of Sertoli, Leydig and germ cells. This study investigates the effect of ERb on the testis using ERb knockout mice (bERKO). Adult male bERKO mice (n=8) and their wild-type littermates (n=7) were killed at 11 weeks postpartum. One testis from each animal was fixed in Bouin’s fluid and embedded. Each testis was fractionated and thick sections cut and stained with PAS. The optical disector method was used to count the number of Leydig cells, Sertoli cells, spermatogonia, spermatocytes and spermatids in each testis. Trunk blood was collected and plasma testosterone concentrations measured by radioimmunoassay. No significant differences in body or testis weight were seen between the bERKO or wild-type mice. Similar numbers of Sertoli cells, spermatogonia, spermatocytes and spermatids were also observed between the two groups. The number of Leydig cells was significantly increased in bERKO mice compared with their wild-type littermates (P < 0.05). Despite the increased number of Leydig cells in the bERKO mice there was no significant difference in plasma testosterone concentrations in this group compared to the wild-type mice. Oestrogen has been reported to inhibit proliferation of adult-type Leydig cells and to inhibit steroidogenesis. This study suggests that the regulation of Leydig cell proliferation may be mediated by ERb. The presence of normal circulating testosterone concentrations in bERKO mice suggests that the effects of oestrogen on steroidogenesis are not brought about by ERbeta.

scholarly journals Probing GATA factor function in mouse Leydig cells via testicular injection of adenoviral vectors

Reproduction ◽  
2017 ◽  
Vol 154 (4) ◽  
pp. 455-467 ◽  
Author(s):  
Gervette M Penny ◽  
Rebecca B Cochran ◽  
Marjut Pihlajoki ◽  
Antti Kyrönlahti ◽  
Anja Schrade ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Function ◽  
Chromatin Condensation ◽  
Adenoviral Vectors ◽  
Lymphoid Cells ◽  
Testicular Atrophy ◽  
Ultrastructural Changes ◽  
Gata Factor

Testicular Leydig cells produce androgens essential for proper male reproductive development and fertility. Here, we describe a new Leydig cell ablation model based on Cre/Lox recombination of mouse Gata4 and Gata6, two genes implicated in the transcriptional regulation of steroidogenesis. The testicular interstitium of adult Gata4flox/flox; Gata6flox/flox mice was injected with adenoviral vectors encoding Cre + GFP (Ad-Cre-IRES-GFP) or GFP alone (Ad-GFP). The vectors efficiently and selectively transduced Leydig cells, as evidenced by GFP reporter expression. Three days after Ad-Cre-IRES-GFP injection, expression of androgen biosynthetic genes (Hsd3b1, Cyp17a1 and Hsd17b3) was reduced, whereas expression of another Leydig cell marker, Insl3, was unchanged. Six days after Ad-Cre-IRES-GFP treatment, the testicular interstitium was devoid of Leydig cells, and there was a concomitant loss of all Leydig cell markers. Chromatin condensation, nuclear fragmentation, mitochondrial swelling, and other ultrastructural changes were evident in the degenerating Leydig cells. Liquid chromatography-tandem mass spectrometry demonstrated reduced levels of androstenedione and testosterone in testes from mice injected with Ad-Cre-IRES-GFP. Late effects of treatment included testicular atrophy, infertility and the accumulation of lymphoid cells in the testicular interstitium. We conclude that adenoviral-mediated gene delivery is an expeditious way to probe Leydig cell function in vivo. Our findings reinforce the notion that GATA factors are key regulators of steroidogenesis and testicular somatic cell survival. Free Finnish abstract: A Finnish translation of this abstract is freely available at http://www.reproduction-online.org/content/154/4/455/suppl/DC2.

Steroid metabolism by a tumour of the specific gonadal stroma in a child

1982 ◽  
Vol 99 (4) ◽  
pp. 624-629 ◽  
Author(s):  
Alicia Barmach de Niepomniszcze ◽  
Marco A. Rivarola ◽  
Héctor E. Chemes ◽  
César Bergadá
Keyword(s):  
Leydig Cell ◽  
Sertoli Cells ◽  
Sexual Development ◽  
Cell Function ◽  
Hydroxysteroid Dehydrogenase ◽  
Steroid Metabolism ◽  
Male Pseudohermaphroditism ◽  
Testosterone Biosynthesis ◽  
Pubertal Boys ◽  
Leydig Cell Function

Abstract. A study of steroid metabolism by a tumour of the specific gonadal stroma was carried out in a 10 year old boy. Tumours developed in the two testes from multiple foci, and clinically, no signs of sexual development were evident. Four testicular enzymes necessary for testosterone biosynthesis were estimated in the child, in two adult controls, and in three pre-pubertal boys with male pseudohermaphroditism but normal tests of Leydig cell function. 17α-Hydroxylase and 17β-hydroxysteroid dehydrogenase were similar in the five controls and in the gonad with the tumour, while 17,20-desmolase and 3β-hydroxysteroid dehydrogenase were grossly deficient in the child with the tumour. These enzyme deficiencies might explain the absence of peripheral virilization in a boy with a tumour of Leydig and Sertoli cells.

scholarly journals Protein kinase G-mediated stimulation of basal Leydig cell steroidogenesis

2007 ◽  
Vol 293 (5) ◽  
pp. E1399-E1408 ◽  
Author(s):  
Silvana A. Andric ◽  
Marija M. Janjic ◽  
Natasa J. Stojkov ◽  
Tatjana S. Kostic
Keyword(s):  
Protein Kinase ◽  
Leydig Cells ◽  
Regulatory Protein ◽  
Nitric Oxide Donor ◽  
Stimulatory Action ◽  
Guanylyl Cyclases ◽  
Androgen Synthesis ◽  
Dependent Protein ◽  
Phosphodiesterase 5 ◽  
Stimulation Of

The androgen-secreting Leydig cells produce cGMP, but the pathways responsible for generation and actions of this intracellular messenger have been incompletely characterized in these cells. Here, we show the presence of mRNA transcripts for the membrane-bound and soluble guanylyl cyclases (sGC), the cGMP-specific phosphodiesterase 5, and the cGMP-dependent protein kinase I (PKG I) and PKG II in purified rat Leydig cells from adult animals. Stimulation of both guanylyl cyclases and inhibition of phosphodiesterase 5 in vitro were accompanied by elevations in cGMP and androgen production, whereas inhibition of sGC and PKG led to a decrease in steroidogenesis. The stimulatory action of cGMP on steroidogenesis was preserved in cells with inhibited cAMP-dependent protein kinases. Experiments with exogenously added substrates revealed the dependence of cGMP-induced progesterone and androgen synthesis on cholesterol but not on 22-OH cholesterol, pregnenolone, progesterone, and Δ4-androstenedione. Treatment with nitric oxide donor increased phosphorylation of the steroidogenic acute regulatory protein (StAR). In contrast, inhibition of sGC and PKG, but not protein kinase A, significantly reduced StAR phosphorylation. These results suggest that cGMP contributes to the control of basal steroidogenesis in Leydig cells through the PKG-dependent modification of the StAR protein.

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