Vincenzo Bonifacio

Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis

Objectives  Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle‐aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile.

Effects of testosterone on sexual function in men: results of a meta‐analysis

Objectives  The role of androgen decline in the sexual activity of adult males is controversial. To clarify whether sexual function would benefit from testosterone (T) treatment in men with partially or severely reduced serum T levels, we conducted a systematic review and meta‐analysis of placebo‐controlled studies published in the past 30 years. The aim of this study was to assess and compare the effects of T on the different domains of sexual life.

A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up

Introduction: The clinical significance of low to low-normal testosterone (T) levels in men remains debated. Aim: To analyze the effects of raising serum T on lean body mass (LBM), fat mass (FM), total body mass, and health-related quality-of-life (HRQoL). Methods: Randomized, double-blind, placebo-controlled study. Men, aged 50–80 years, with serum total T<15 nmol/L and bioavailable T < 6.68 nmol/L, and a Aging Males’ Symptoms (AMS) total score >36, received 6 months treatment with transdermal 1% T gel (5–7.5 mg/day; n =183) or placebo gel (n =179), followed by 12 months open-label with T in all. Results: After 6 months, LBM increased in T- treated patients by 1.28 ± 0.15 kg (mean ± SE) and FM decreased by 1.16 ± 0.16 kg, with minor changes with placebo (LBM +0.02 ± 0.10 kg and FM −0.14 ± 0.12 kg; all p < 0.001, T group vs. placebo). Changes were largely similar across subgroups of age, baseline total testosterone, and baseline BMI. Total HRQoL improved compared with placebo (p < 0.05, T group vs. placebo). Conclusions: Six months 1% T gel improved body composition and HRQoL in symptomatic men with low to low-normal T, with further improvements over the following 12 months.

Immunohistochemical localization of growth hormone-releasing hormone in human gonads

Human gonads were examined for the presence of ir growth hormone-releasing-hormone. We demonstrated the presence of immu-nostainable cells both in ovarian and in testicular tissue using a non-crossreactive antiGRH antiserum and the immunoperoxidase detection technique. In ovaries from ovulating women, GRH immunoreactivity was localized in the corpórea lutea; granulosa cells, theca cells and cells of primary follicles did not stain. In premenopausal ovaries, staining was detectable in scattered luteinized stromal cells. In testes from post-puberal men GRH immunoreactivity was localized in the Leyding cells; cells of the germinal epithelium did not stain. These results demonstrate the presence of GRH in human gonads and suggest that this peptide may exert regulatory function at the testicular and ovarian levels.

Naloxone increases bioactive LH in man: evidence for selective release of early LH pool.

Opioid peptides inhibit LH secretion and the opiate antagonist naloxone provokes increases in plasma LH levels by release of endogenous GnRH from the hypothalamus. To explore the effect of endogenously released GnRH on the mobilization of bioactive LH pools, the bioactive LH response to a single iv bolus dose of 20 mg naloxone has been evaluated and compared to the immunoactive pattern of the hormone in eight young normal male volunteers. Blood samples were withdrawn at 15, 30, 45, 60, 90, 120 min after naloxone injection and LH levels were measured by RIA and rat interstitial cell testosterone (RICT) bioassay. A significant increase in both bio and immuno active LH was observed in all subjects after 15–30 min (p < 0.05 to p < 0.001), reaching maximal levels at 30–60 min for both forms of the hormone. The time course of the bioactive LH response magnified the immunoactive LH pattern, and the maximum fold increases were 1.4 and 1.3 fold (62.4 ± 5.5 SE and 25.0 ± 3.7 SE mlU/ml) from basal bio and immuno LH levels of 25.9 ± 4.3 SE and 11.1 ± 2.0 SE mlU/ml respectively. An early single peak response of bio and immunoactive LH was observed in six subjects while a biphasic pattern was observed in two subjects with a clearly defined and prominent early pool followed by a second pool of higher magnitude. Both bio and iummunoactive LH levels began to decline at 45–60 min, but in most subjects remained significantly elevated by about 30% above the basal values at 120 min. The finding of a significant early bioactive LH increase gives further support to the clinical use of naloxone as a test to investigate the hypothalamic function in man.

Androgen modulation of pro-inflammatory and anti-inflammatory cytokines during preadipocyte differentiation.

Abstract Background: Macrophages and adipocytes contribute to release of cytokines resulting in the chronic inflammatory profile of the metabolic syndrome. The local increase of proinflammatory cytokines impairs adipogenesis, resulting in formation of dysfunctional adipocytes that are unable to store and handle lipids. The altered lipid fluxes in/from adipocytes affect whole-body metabolism. We investigated the role of androgens on adipocyte-derived proinflammatory and anti-inflammatory cytokines during preadipocyte differentiation. Materials and methods: Various differentiation methods were used to obtain full conversion of 3T3-L1 into mature adipocytes. The degree of adipocyte conversion in the presence/absence of dihydrotestosterone (DHT) was analyzed by measuring intracellular triglycerides (Oil Red O staining). The effects of DHT administration on interleukin 1β (IL-1β), IL-2, IL-6, IL-10, IL-12, interferon γ (IFNγ) and tumor necrosis factor α (TNFα) secretion was measured at days 0, 4, 6 and 8 of differentiation using the SearchLight multiplex protein array. Results: DHT regulates a number of cytokines in committed and mature 3T3-L1 adipocytes. IL-1β and TNFα were readily suppressed at the very early stages of differentiation. IFNγ release was inhibited at day 4, but the effect was no longer detectable on day 8. IL-6 and IL-12 were significantly reduced at day 8 of differentiation. Conversely, the differentiation-dependent increase of IL-2 and IL-10 was further stimulated by DHT since day 0. Conclusions: We provide evidence that androgens promote an anti-inflammatory profile that parallels the acquisition of a functional adipocyte phenotype. The crosstalk between androgens, adipocyte-derived mediators of inflammation and intracellular lipid fluxes could have profound implications on metabolism of men with obesity and metabolic syndrome.

Bombesin‐like Immunoreactivity in Human Seminal Fluid

Bombesin is a tetradecapeptide isolated from the skin of the frog Bombina bombina.’ Immunoreactivity to bombesin has been found in normal’ and neoplastic3 mammalian tissues, as well as in human milk,’ cerebrospinal fluid,’ and alveolar macrophages.6 Recently, it has been reported that a considerable percentage of prostatic cells contain bornbesin-like immunoreactivity.’ Since the localization of a peptide along the male reproductive tract suggests the presence of the substance in seminal secretions, we sought to determine whether human seminal fluid could be a source of bombesin-like peptides.

Isolation of a human seminal plasma peptide with bombesin-like activity**Presented in part at the 70th Annual Meeting of the Endocrine Society, New Orleans, Lousiana, June 8 to 11, 1988.

Bombesin (BN) and BN-like peptides such as gastrin-releasing peptide (GRP) belong to the growing group of regulatory peptides. Bombesin and GRP share the same carboxyl-terminal heptapeptide sequence that is essential for receptor recognition and biologic activity. Immunohistochemical findings have indicated the presence of a BN-like peptide in the neuroendocrine cells of the human prostate. These findings, together with the high concentrations of different regulatory peptides recently found in seminal plasma, prompted us to characterize a BN-like peptide in human semen by gel-filtration chromatography, reverse-phase high-pressure liquid chromatography, and in vitro bioassay. Here we demonstrate that human semen contains high levels (mean +/- standard deviation, 288.9 +/- 114.39 pg/ml) of a substance that closely resembles the 14-27 carboxyl-terminal fragment of GRP (GRP 14-27). The partially purified peptide obtained from this source, examined on an in vitro bioassay that is especially useful for testing BN-like activities, elicits a contractile response of the rat uterus that is indistinguishable from that stimulated by standard BN and GRP 14-27. The GRP 14-27 present in human seminal plasma may be involved in some aspect of the process of fertilization.