giovedì, Luglio 18, 2024

Metodiche ecografiche per la diagnosi e la gestione temporale del tumore epatico

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Acido folico nella biologia e nella pratica: per l’anemia, la riproduzione e non solo

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Testosterone comes to age: polyphenols and their food sources as possible “virility” boosters

Male hormones and how they are regulated

Androgens are produced primarily by Leydig cells in the testes and are vital for the development and maintenance of male sexual organs and secondary sexual characteristics. Testosterone stimulates the development of male reproductive structures in the embryo and plays key roles during puberty, including spermatogenesis and gonadotropin regulation. Testosterone production declines about 1% per year starting in the thirties, leading to late-onset hypogonadism characterized by reduced libido, muscle mass, and bone density, among other symptoms. Leydig cells are responsible for the biosynthesis of testosterone in the testis and use cholesterol as a precursor.

They also produce androstenedione and dehydroepiandrosterone (DHEA), although these hormones are less effective at activating the androgen receptor. Steroidogenesis in Leydig cells is mainly regulated by luteinizing hormone (LH), which activates the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, influencing the expression of steroidogenic enzymes. PKA substrates include STAR, which is critical for the transport of cholesterol into mitochondria, and several transcription factors that regulate the expression of steroidogenic genes (e.g. SREBP-2). Other signaling pathways, such as mitogenic protein kinases (MAPK), calcium-dependent protein kinases (PKC and CAMK), and the JAK/STAT pathway also play a role in this regulation.

The problem of age-related hypogonadism

Testosterone is critical for maintaining muscle mass, bone density, sexual function, energy levels, metabolic health, cognitive function, and overall male well-being. As men age and testosterone levels decline, they may experience sarcopenia, indicated by bone mineral density, reduced libido, erectile dysfunction, fatigue and cognitive decline. Maintaining adequate testosterone levels is essential for male health and well-being. Late-onset male hypogonadism is characterized by a decline in testosterone production due to aging, which is generally treated with replacement therapy, which can have side effects due to negative feedback on the hypothalamus and pituitary gland. Although at a certain age the problem of fertility no longer arises, maintaining muscle mass and cognitive functions remains central. It is important to remember, then, that the use of statins to lower cholesterol, for the purposes of cardiovascular prevention, is not often considered but potentially removes substrate for the production of androgens.

Natural antioxidants and androgen production

Action of flavonoids

Flavonoids can be divided into flavanones, flavones, flavonols and anthocyanidins. They have been associated with numerous health benefits, including cancer prevention and reduced risk of cardiovascular and neurodegenerative diseases. Flavones such as luteolin and apigenin, found in celery, fennel, yellow peppers, cucumbers, parsley and thyme, can stimulate the expression of steroidogenic genes and increase androgen production in Leydig cells. Soy and chickpea isoflavones, such as genistein and daidzein, can interfere with estrogen signaling in the testicles. High concentrations of isoflavones can reduce steroidogenesis in Leydig cells. While some studies suggest that isoflavones lower testosterone levels, others indicate no significant effects.

Effects of flavonols and anthocyanins

Flavonols such as quercetin and myricetin, present in berries, apples and tea, improve steroidogenesis and testicular function. Quercetin improves testosterone levels in male mice exposed to endocrine disruptors. However, its effects on testosterone synthesis can vary from species to species. Flavanones such as naringenin, found in grapefruits, can increase serum testosterone levels and prevent testosterone decline caused by endocrine disruptors. Catechins in apples, cocoa, red wine and tea can increase plasma testosterone levels in male rats. However, some studies have reported that green tea polyphenols inhibit androgen synthesis. Anthocyanidins (top represented in berries, dark grapes, and eggplants) can enhance steroidogenesis by inhibiting cyclooxygenase-2 (COX2) and modulating MAPK signaling.

Conclusions

To summarize, plasma levels of natural polyphenolic compounds in the micromolar range can be achieved with a rich and varied diet of fruits and vegetables, supporting optimal Leydig cell function. In addition to flavones, in fact, there are also other food polyphenols that can have similar functions. Phenolic acids such as sinapic acid (citrus fruits, berries and various spices) and CAPE from propolis can increase androgen production by enhancing the expression of genes related to steroidogenesis in Leydig cells. Finally, resveratrol in grapes, red wine and hazelnuts improves spermatogenesis and testosterone production but may inhibit androgen production in some conditions. This does not depend on the quantities of wine consumed, but the context of the quantities of alcohol consumed.

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Pubblicazioni scientifiche

Martin LJ, Touaibia M. Nutrients 2024; 16(12):1815.

Basque A et al. Toxicol In Vitro. 2023 Feb; 86:105505.

Martin LJ, Touaibia M. Antioxidants. 2020; 9(3):237

Cormier M et al. Cell Biol Toxicol. 2018; 34(1):23-38.

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Dott. Gianfrancesco Cormaci
Dott. Gianfrancesco Cormaci
Laurea in Medicina e Chirurgia nel 1998, specialista in Biochimica Clinica dal 2002, ha conseguito dottorato in Neurobiologia nel 2006. Ex-ricercatore, ha trascorso 5 anni negli USA alle dipendenze dell' NIH/NIDA e poi della Johns Hopkins University. Guardia medica presso la casa di Cura Sant'Agata a Catania. In libera professione, si occupa di Medicina Preventiva personalizzata e intolleranze alimentari. Detentore di un brevetto per la fabbricazione di sfarinati gluten-free a partire da regolare farina di grano. Responsabile della sezione R&D della CoFood s.r.l. per la ricerca e sviluppo di nuovi prodotti alimentari, inclusi quelli a fini medici speciali.

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