scholarly journals Growing Up Under Constant Light: A Challenge to the Endocrine Function of the Leydig Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Dijana Z. Marinkovic ◽  
Marija L. J. Medar ◽  
Alisa P. Becin ◽  
Silvana A. Andric ◽  
Tatjana S. Kostic
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Mitochondrial Dynamics ◽  
Positive Element ◽  
Endocrine Function ◽  
Constant Light ◽  
Mtdna Copy Number ◽  
Voluntary Activity ◽  
Genes Encoding ◽  
Negative Effect

The factors influencing Leydig cell maturity and the acquisition of functional capacity are incompletely defined. Here we analyzed the constant light (LL) influence on Leydig cells’ endocrine function during reproductive maturation. Rats were exposed to LL from P21 to P90. Data were collected at juvenile (P35), peri/pubertal (P42, P49), and adult (P90) stages of life. The results proved the effect of LL on rats’ physiology by changing of bimodal voluntary activity pattern into free-running. Additionally, the peripheral clock in Leydig cells changed in LL condition, indicating disturbed rhythm: the positive element (Bmal1) increased in pre-/pubertal but decreased in the adult period, while negative elements (Per2 and Reverba) were increased. The effects of LL were most prominent in puberty: pituitary genes encoding gonadotropic hormones (Cga, Lhb, Fshb) decreased; serum corticosterone increased, while serum androgens and mass of testicular and sex accessory organs reduced; markers of Leydig cells maturity/differentiation (Insl3, Lhcgr) and steroidogenesis-related genes (Scarb1, Star, Cyp11a1, Cyp17a1) decreased; the steroidogenic and energetic capacity of the Leydig cell mitochondria decreased; the mtDNA copy number reduced, and mitochondrial dynamics markers changed: fusion decreased (Opa1 and Mfn2), and mitophagy increased (Pink1). In adults, the negative effect of LL on mitochondrial function and steroidogenic capacity persists in adult Leydig cells while other parameters reached control values. Altogether, the results indicate that LL slows down Leydig cells’ maturation by reducing the endocrine and energy capacity of cells leading to the delay of reproductive development.

INSL3: A Marker of Leydig Cell Function and Testis-Bone-Skeletal Muscle Network

2020 ◽  
Vol 27 (12) ◽  
pp. 1246-1252
Author(s):  
Paolo Facondo ◽  
Andrea Delbarba ◽  
Filippo Maffezzoni ◽  
Carlo Cappelli ◽  
Alberto Ferlin
Keyword(s):  
Skeletal Muscle ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Function ◽  
Cell Damage ◽  
Endocrine Function ◽  
Testicular Descent ◽  
Male Hypogonadism ◽  
Adult Men ◽  
Leydig Cell Function

This article reviews the role of INSL3 as biomarker of Leydig cell function and its systemic action in testis-bone-skeletal muscle crosstalk in adult men. Insulin-like factor 3 (INSL3) is a peptide hormone secreted constitutively in a differentiation-dependent mode by testicular Leydig cells. Besides the role for the testicular descent, this hormone has endocrine anabolic functions on the bone-skeletal muscle unit. INSL3 levels are low in many conditions of undifferentiated or altered Leydig cell status, however the potential clinical utility of INSL3 measurement is not yet well defined. INSL3 levels are modulated by the long-term cytotropic effect of the hypothalamicpituitary- gonadal axis, unlike testosterone that is acutely sensitive to the stimulus by luteinizing hormone (LH). INSL3 directly depends on the number and differentiation state of Leydig cells and therefore it represents the ideal marker of Leydig cell function. This hormone is more sensitive than testosterone to Leydig cell impairment, and the reduction of INSL3 in adult men can precociously detect an endocrine testicular dysfunction. Low INSL3 levels could cause or contribute to some symptoms and signs of male hypogonadism, above all sarcopenia and osteoporosis. The measurement provided suggested that the measurement of INSL3 levels should be considered in the clinical management of male hypogonadism and in the evaluation of testicular endocrine function. The monitoring of INSL3 levels could allow an early detection of Leydig cell damage, even when testosterone levels are still in the normal range.

On the Function of the Interstitium of the Testis

1949 ◽  
Vol s3-90 (11) ◽  
pp. 265-280
Author(s):  
A. J. MARSHALL
Keyword(s):  
Connective Tissue ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Secretory Component ◽  
Endocrine Function ◽  
Pigment Cells ◽  
Maximum Diameter ◽  
Breeding Area ◽  
Anatomical Basis ◽  
Tissue Cells

1. An investigation of the seasonal cycle of the interstitium of the testes of birds, based on sixty-four individuals of varying age, has been carried out on the fulmar petrel, Fulmaris glacialis (L.). 2. The following cells (see diagram, p. 268) occur: (i) Fibroblasts of the sheaths of tubules, blood-vessels, and of groups of Leydig cells. (ii) Pigment cells. (iii) Juvenile Leydig cells (generally containing lipoid droplets). (iv) Lipoid Leydig cells. (v) Fuchsinophil Leydig cells. (vi) Areolar connective-tissue cells. 3. In the young bird the juvenile cell develops into the lipoid Leydig cell at a time when the testis-tubules also indicate approaching sexual maturity. In the adult, the interstitium generally consists for the most part of lipoid Leydig cells. These exhibit mitochondria when the soluble lipoids are removed by embedding in wax. At the height of spermatogenesis, and at the beginning of epithelial breakdown and tubule-regression, most of the Leydig cells have lost much of their lipoids and some of them exhibit increasing amounts of fuchsinophil substances, as described by Benoit. A fuchsinophil cell thus appears. 4. The Lipoid cell at all seasons shows a positive Schultz reaction (for cholesterol), which corresponds in intensity to the amount of sudanophil material present. It has not been possible to demonstrate cholesterol in the fuchsinophil cell. 5. At the time when the tubules are at their maximum diameter and their degeneration is under way, mitochondria are at the greatest abundance in the Leydig cell. At this period a new generation of Leydig cells arises in the interstitium. These cells quickly become meagrely sudanophil and resemble the sudanophil juvenile cells of the immature bird. They are Schultz positive. The tubules collapse; the new Leydig generation fills the empty interstitium. They exhibit profuse mitochondria, gain in lipoid content and so the interstitium is regenerated. 6. The exhausted tubules undergo a fatty metamorphosis at the time of their collapse; at the period when the interstitium has little lipoid the tubules are full of it. Beneath this fat (also Schultz positive) arises a new tubule-epithelium. The tubules as well as the interstitium are regenerated while the young of the next generation are still in the nests. An anatomical basis for an internal physiological rhythm may thus have been shown. 7. The new interstitial cells are already heavily lipoidal and the new tubule epithelium contains spermatogonia when the petrels move seaward away from the breeding cliffs in the autumn. They return to the breeding area in November and December. Thus testis regeneration, and movement both away from and back to the breeding area, occurs while the days are getting shorter. 8. From the time the birds appear on the breeding cliffs (and apparently since the autumn) there is an increase in lipoid cells along with heightened sexuality as revealed by the ripening tubule-products. These supplementary lipoid Leydig cells seem to develop from the small non-sudanophil areolar connective-tissue cells which are prominent in the adult interstitium. 9. Whilst it is not denied that the fuchsinophil cell (‘secretory cell’ of Sluiter and van Oordt) may have an endocrine function, the present results suggest that the lipoid Leydig cell is the primary secretory component of the avian testis. When the interstitium, after reproduction, passes once more to a lipoidal phase, it is not losing its secretory function as Sluiter and van Oordt infer, but is regenerating in readiness for the next season's breeding activities.

Effects of pure FSH and LH preparations on the number and function of Leydig cells in immature hypophysectomized rats

1989 ◽  
Vol 120 (1) ◽  
pp. 97-NP ◽  
Author(s):  
K. J. Teerds ◽  
J. Closset ◽  
F. F. G. Rommerts ◽  
D. G. de Rooij ◽  
D. M. Stocco ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Esterase Activity ◽  
Leydig Cells ◽  
Major Effect ◽  
Plasma Testosterone ◽  
Negative Effect ◽  
Hypophysectomized Rats ◽  
And Function

ABSTRACT The effects of pure FSH and/or LH preparations on the number of Leydig cells and their function in immature hypophysectomized rats have been investigated. As a result of hypophysectomy at the age of 17–18 days, the number of recognizable Leydig cells per testis decreased, as did the steroidogenic capacity in vivo and in vitro. Treatment with 64 μg FSH on both 22 and 23 days of age, did not affect the number of recognizable Leydig cells. In contrast, two injections of LH (10 μg) caused a sixfold increase in the number of Leydig cells, but had a negative effect on spermatogenesis. These stimulatory and inhibitory effects of LH diminished when FSH was added. Treatment with FSH for 7 days caused a twofold increase in the number of Leydig cells when compared with hypophysectomized controls. 3β-Hydroxysteroid dehydrogenase (3β-HSD) and esterase activity in Leydig cells also increased under the influence of FSH. The pregnenolone production per Leydig cell in the presence of 5-cholesten-3β,22(R)-diol (22R-hydroxycholesterol) as substrate showed a sevenfold increase. Plasma testosterone levels 2 h after injection of human chorionic gonadotrophin in intact rats and hypophysectomized FSH-treated rats were the same. Following LH treatment for 7 days, the number of Leydig cells proved to be 11 times higher, and 3β-HSD and esterase activity were not different from intact controls. The testicular pregnenolone production was four- to fivefold higher when compared with untreated hypophysectomized rats. However, pregnenolone production per Leydig cell in LH-treated rats was only slightly different from the hypophysectomized controls. In conclusion, FSH treatment caused an increase in the number and steroidogenic activity of Leydig cells, and LH had a major effect on the number of Leydig cells, but did not stimulate the steroidogenic capacity. Journal of Endocrinology (1989) 120, 97–106

scholarly journals Male 41, XXY* Mice as a Model for Klinefelter Syndrome: Hyperactivation of Leydig Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2898-2910 ◽  
Author(s):  
Joachim Wistuba ◽  
C. Marc Luetjens ◽  
Jan-Bernd Stukenborg ◽  
Andreas Poplinski ◽  
Steffi Werler ◽  
...  
Keyword(s):  
Germ Cell ◽  
X Chromosome ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Function ◽  
Klinefelter Syndrome ◽  
Cell Loss ◽  
Endocrine Function ◽  
Maximal Response ◽  
Different Ages

Sex chromosome imbalance in males is linked to a supernumerary X chromosome, a condition resulting in Klinefelter syndrome (KS; 47, XXY). KS patients suffer from infertility, hypergonadotropic hypogonadism, and cognitive impairments. Mechanisms of KS pathophysiology are poorly understood and require further exploration using animal models. Therefore, we phenotypically characterized 41, XXY* mice of different ages, evaluated observed germ cell loss, studied X-inactivation, and focused on the previously postulated impaired Leydig cell maturation and function as a possible cause of the underandrogenization seen in KS. Xist methylation analysis revealed normal X-chromosome inactivation similar to that seen in females. Germ cell loss was found to be complete and to occur during the peripubertal phase. Significantly elevated FSH and LH levels were persistent in 41, XXY* mice of different ages. Although Leydig cell hyperplasia was prominent, isolated XXY* Leydig cells showed a mature mRNA expression profile and a significantly higher transcriptional activity compared with controls. Stimulation of XXY* Leydig cells in vitro by human chorionic gonadotropin indicated a mature LH receptor whose maximal response exceeded that of control Leydig cells. The hyperactivity of Leydig cells seen in XXY* mice suggests that the changes in the endocrine milieu observed in KS is not due to impaired Leydig cell function. We suggest that the embedding of Leydig cells into the changed testicular environment in 41 XXY* males as such influences their endocrine function.

Androgen receptor signalling in testicular Leydig cells is essential for Leydig cell maturation and survival

2014 ◽  
Author(s):  
Laura O'Hara ◽  
Kerry McInnes ◽  
Ioannis Simitsidellis ◽  
Steph Morgan ◽  
Laura Milne ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Maturation ◽  
Receptor Signalling

scholarly journals The Leydig Cell MEK/ERK Pathway Is Critical for Maintaining a Functional Population of Adult Leydig Cells and for Fertility

2011 ◽  
Vol 25 (7) ◽  
pp. 1211-1222 ◽  
Author(s):  
Soichi Yamashita ◽  
Ping Tai ◽  
Jean Charron ◽  
CheMyong Ko ◽  
Mario Ascoli
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Erk Pathway ◽  
Adult Leydig Cells

A review of drug-induced Leydig cell hyperplasia and neoplasia in the rat and some comparisons with man

1995 ◽  
Vol 14 (7) ◽  
pp. 562-572 ◽  
Author(s):  
DE Prentice ◽  
AW Meikle
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Safety Assessment ◽  
Hormonal Status ◽  
Control Mechanisms ◽  
Hormone Production ◽  
Drug Induced ◽  
Cell Hyperplasia ◽  
Etiological Factors ◽  
Func Tion

This paper describes control of normal Leydig cell func tion and testosterone production. The macroscopic and histopathological appearances of spontaneous Leydig cell hyperplasias and tumors (LCT) in the rat are reviewed together with their incidence and hormonal status. Drugs which induce LCTs in chronic studies are discussed and include busereline, carbamazepine, cimetidine, finas teride, flutamide, gemfibrozil, histrelin, hydralazine, indomethacin, isradipine, lactitol, leuprolide, metronida zole, mesulergine, nafarelin, norprolac and vidarabine. The known mechanisms of LCT induction in the rat are reviewed together with other possible etiological factors. The incidence, clinical picture and etiological factors of LCTs in man are also surveyed. Hormone production in Leydig cells and LCTs in rats and man are compared. Differences between the two species are considered, par ticularly with regard to Leydig cell control mechanisms. The paper concludes that drug-induced LCTs in rats are most probably not predictive for man and their occurrence has little relevance in human safety assessment.

scholarly journals Variability in mitochondrial import, mitochondrial health and mtDNA copy number using Type II and Type V CRISPR effectors

2020 ◽  
Author(s):  
Zuriñe Antón ◽  
Grace Mullally ◽  
Holly Ford ◽  
Marc W. van der Kamp ◽  
Mark D. Szczelkun ◽  
...  
Keyword(s):  
Mitochondrial Genome ◽  
Copy Number ◽  
Protein Targeting ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Protein ◽  
Mitochondrial Diseases ◽  
Basic Research ◽  
Strategy Development ◽  
Mtdna Copy Number ◽  
Mitochondrial Import

ABSTRACTCurrent methodologies for targeting the mitochondrial genome for basic research and/or therapeutic strategy development in mitochondrial diseases are restricted by practical limitations and technical inflexibility. The development of a functional molecular toolbox for CRISPR-mediated mitochondrial genome editing is therefore desirable, as this could enable precise targeting of mtDNA haplotypes using the precision and tuneability of CRISPR enzymes; however, published reports of “MitoCRISPR” systems have, to date, lacked reproducibility and independent corroboration. Here, we have explored the requirements for a functional MitoCRISPR system in human cells by engineering several versions of CRISPR nucleases, including the use of alternative mitochondrial protein targeting sequences and smaller paralogues, and the application of gRNA modifications that reportedly induce mitochondrial import. We demonstrate varied mitochondrial targeting efficiencies and influences on mitochondrial dynamics/function of different CRISPR nucleases, with Lachnospiraceae bacterium ND2006 (Lb) Cas12a being better targeted and tolerated than Cas9 variants. We also provide evidence of Cas9 gRNA association with mitochondria in HeLa cells and isolated yeast mitochondria, even in the absence of a targeting RNA aptamer. Finally, we present evidence linking mitochondrial-targeted LbCas12a/crRNA with increased mtDNA copy number dependent upon DNA binding and cleavage activity. We discuss reproducibility issues and the future steps necessary if MitoCRISPR is to be realised.

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