International Journal of Molecular Sciences

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Dear Colleagues,

During the last several decades male sexual function has been rapidly decreasing in terms of both steroidogenesis and spermatogenesis. Due to changes of lifestyle and increased pollution, every year more men suffer from hypogonadism and infertility.

The complex process of reproduction is finely regulated by various factors, including autocrine, paracrine, juxtracrine and endocrine environments within the gonads. All these processes are inter-connected to each other, and the major role is performed by the sex hormones.

Testes perform two important roles in one unit: they produce testosterone (steroidogenesis) and maintain germ cell development. Sertoli cells play the key role in terms of male fertility regulating hormones and producing signaling molecules, including growth factors and inflammatory cytokines which are involved in and sustain the process of spermatogenesis.

The aim of this Special Issue is to identify new pathways involved in the mechanisms of both steroidogenesis and spermatogenesis in order to maintain sexual function, and to prevent and cure infertility and hypogonadism.

In this Special Issue, we encourage authors to submit original research papers or review articles focused on the following topics:

Endocrine function of the testis;
Hormones and fertility;
Male hypogonadism;
Signaling molecules and spermatogenesis;
Endocrine disruptors and testicular function;
Androgens and molecular pathways.

Prof. Dr. Davide Francomano
Guest Editor

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Keywords

male hormones
male sexual function
testosterone
endocrine function of the testis
hormones
fertility

Published Papers (1 paper)

Research

16 pages, 2368 KiB

Open AccessArticle

Plasma Metabonomics in Insulin-Resistant Hypogonadic Patients Induced by Testosterone Treatment

by Lello Zolla, Giuseppe Grande and Domenico Milardi

Int. J. Mol. Sci. 2022, 23(14), 7754; https://doi.org/10.3390/ijms23147754 - 14 Jul 2022

Cited by 5 | Viewed by 1633

Abstract

Hypogonadic subjects with insulin resistance (IR) showed different metabonomic profiles compared to normo-insulinemic subjects (IS). Testosterone replacement therapy (TRT) may have a different impact on the metabolisms of those with the presence or absence of insulin resistance. We evaluated the changes in the metabolism of IR hypogonadic patients before and after 60 days of TRT. The metabonomic plasma profiles from 20 IR hypogonadal patients were recorded using ultra-high-performance liquid chromatography (UHPLC) and high-resolution mass spectrometry (HRMS). Plasma metabolites, before and after 60 days of TRT, were compared. In hypogonadic patients, carnosine, which is important for improving performance during exercise, increased. Conversely, proline and lysine—amino acids involved in the synthesis of collagen—reduced. Triglycerides decreased and fatty acids (FFAs) increased in the blood as a consequence of reduced FFA β-oxidation. Glycolysis slightly improved, while the Krebs cycle was not activated. Gluconeogenesis (which is the main energy source for hypogonadal IR before TRT) stopped after treatment. As a consequence, lactate and acetyl CoA increased significantly. Both lactate and acetyl CoA were metabolized into ketone bodies which increased greatly, also due to leucine/isoleucine degradation. Ketone bodies were derived predominantly from acetyl CoA because the reaction of acetyl CoA into ketone bodies is catalyzed by mtHMGCoA synthase. This enzyme is inhibited by insulin, which is absent in IR patients but overexpressed following testosterone administration. Ketosis is an alternative route for energy supply and provides the same metabolic effects as insulin but at the metabolic or primitive control level, which bypasses the complex signaling pathway of insulin. After treatment, the hypogonadic patients showed clinical symptoms related to ketonuria. They presented similarly to those following a ketogenic diet, the so-called ‘keto flu’. This must be taken into account before the administration of TRT to hypogonadic patients. Full article

(This article belongs to the Special Issue Molecular Research of Male Hormones)

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