AUTHOR=Marinkovic Dijana Z. , Medar Marija L. J. , Becin Alisa P. , Andric Silvana A. , Kostic Tatjana S. 

TITLE=Growing Up Under Constant Light: A Challenge to the Endocrine Function of the Leydig Cells

JOURNAL=Frontiers in Endocrinology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.653602

DOI=10.3389/fendo.2021.653602

ISSN=1664-2392

ABSTRACT=<p>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 (<italic>Bmal1</italic>) increased in pre-/pubertal but decreased in the adult period, while negative elements (<italic>Per2</italic> and <italic>Reverba</italic>) were increased. The effects of LL were most prominent in puberty: pituitary genes encoding gonadotropic hormones (<italic>Cga, Lhb, Fshb</italic>) decreased; serum corticosterone increased, while serum androgens and mass of testicular and sex accessory organs reduced; markers of Leydig cells maturity/differentiation (<italic>Insl3</italic>, <italic>Lhcgr</italic>) and steroidogenesis-related genes (<italic>Scarb1, Star, Cyp11a1, Cyp17a1</italic>) decreased; the steroidogenic and energetic capacity of the Leydig cell mitochondria decreased; the mtDNA copy number reduced, and mitochondrial dynamics markers changed: fusion decreased (<italic>Opa1</italic> and <italic>Mfn2</italic>), and mitophagy increased (<italic>Pink1</italic>). 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.</p>