Short-term effects of follicle-stimulating hormone on immune function, lipid, and vitamin metabolism in transiently
Background:
Prostate cancer therapy with surgical or chemical castration with gonadotropin-releasing hormone (GnRH) agonists has been linked to elevated follicle-stimulating hormone (FSH) levels, which may contribute to secondary health disorders, including atherosclerosis and diabetes. Although recent findings suggest a role for FSH beyond the reproductive system, its metabolic impact remains unclear and difficult to disentangle from that of androgens. In this study, we examined the metabolic changes induced by FSH and distinguished them from those caused by testosterone.
Methods:
Plasma samples from temporarily medically castrated young men (n = 33) treated with FSH and/or testosterone were characterized by proteomics and metabolomics approaches. All subjects received GnRH antagonists. Sixteen men were randomized to recombinant FSH (300 IU 3 times/week) for 5 weeks, while seventeen men served as controls. After 3 weeks, all men received 1000 mg intramuscular testosterone undecanoate. Blood samples were collected at the start, after 3 weeks and after 5 weeks. The proteome and metabolome signatures were characterized in all samples.
Results:
FSH significantly upregulates key proteins involved in the modulation of inflammatory response and innate immune system (P ≤ 0.03) and dysregulates lipid metabolism, evidenced by downregulation of multiple apolipoproteins (P ≤ 0.04) and increased levels of cholesterol and glycerophospholipids (P ≤ 0.03). In addition, low FSH levels were correlated with a reduction in the active form of vitamin D (P < 0.02). These results highlight the short-term metabolic impacts of FSH in males.
Conclusions And Clinical Implications:
Our findings underlined the FSH effect on extragonadal systems and its connection to metabolic disorders often seen as secondary effects of prostate cancer treatment.
Insights
Follicle-stimulating hormone (FSH) significantly impacts male metabolism, affecting inflammation and lipid profiles. This research clarifies FSH
Area of Science:
- Endocrinology
- Metabolomics
- Proteomics
Background:
- Prostate cancer treatments involving gonadotropin-releasing hormone (GnRH) agonists can elevate follicle-stimulating hormone (FSH) levels.
- Elevated FSH is linked to secondary health issues like atherosclerosis and diabetes.
- The extragonadal metabolic effects of FSH are not well understood, especially differentiating them from androgen effects.
Purpose of the Study:
- To investigate the specific metabolic changes induced by FSH in males.
- To distinguish the metabolic impact of FSH from that of testosterone.
Main Methods:
- Utilized proteomics and metabolomics on plasma samples from medically castrated young men (n=33).
- Subjects received GnRH antagonists, with a subset randomized to recombinant FSH (300 IU 3x/week for 5 weeks).
- Testosterone undecanoate (1000 mg IM) was administered after 3 weeks; blood samples collected at baseline, 3, and 5 weeks.
Main Results:
- FSH upregulated proteins involved in inflammation and innate immunity (P ≤ 0.03).
- FSH dysregulated lipid metabolism, decreasing apolipoproteins (P ≤ 0.04) and increasing cholesterol and glycerophospholipids (P ≤ 0.03).
- Low FSH levels correlated with reduced active vitamin D (P < 0.02).
Conclusions:
- FSH has significant short-term extragonadal metabolic effects in males.
- Findings link FSH to metabolic disorders observed as side effects of prostate cancer therapy.
- Highlights the importance of FSH in metabolic regulation beyond reproductive functions.
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