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- Title
Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men.
- Authors
Abbara, Ali; Narayanaswamy, Shakunthala; Izzi-Engbeaya, Chioma; Comninos, Alexander N.; Clarke, Sophie A.; Malik, Zainab; Papadopoulou, Deborah; Clobentz, Ailish; Sarang, Zubair; Bassett, Paul; Jayasena, Channa N.; Dhillo, Waljit S.
- Abstract
<bold><italic>Background:</italic></bold> Male testosterone levels decline by 1% per year from the age of 40 years. Whilst a primary testicular deficit occurs, hypothalamic or pituitary dysregulation may also coexist. This study aimed to compare the hypothalamic response to kisspeptin-54 and the pituitary response to gonadotropin-releasing hormone (GnRH) of older men with those of young men. <bold><italic>Methods:</italic></bold> Following 1 h of baseline sampling, healthy older men (<italic>n</italic> = 5, mean age 59.3 ± 2.9 years) received a 3-h intravenous infusion of either vehicle, kisspeptin-54 0.1, 0.3, or 1.0 nmol/kg/h or GnRH 0.1 nmol/kg/h, on five different study days. Serum gonadotropins and total testosterone were measured every 10 min and compared to those of young men (<italic>n</italic> = 5/group) (mean age 28.9 ± 2.0 years) with a similar body mass index (24 kg/m2) who underwent the same protocol. <bold><italic>Results:</italic></bold> Kisspeptin-54 and GnRH significantly stimulated serum gonadotropin release in older men compared to vehicle (<italic>p</italic> < 0.001 for all groups). Gonadotropin response to kisspeptin-54 was at least preserved in older men when compared to young men. At the highest dose of kisspeptin-54 (1.0 nmol/kg/h), a significantly greater luteinising hormone (LH) (<italic>p</italic> = 0.003) response was observed in older men. The follicle-stimulating hormone (FSH) response to GnRH was increased in older men (<italic>p</italic> = 0.002), but the LH response was similar (<italic>p</italic> = 0.38). Serum testosterone rises following all doses of kisspeptin-54 (<italic>p</italic> ≤ 0.009) were reduced in older men. <bold><italic>Conclusions:</italic></bold> Our data suggest that healthy older men without late-onset hypogonadism (LOH) have preserved hypothalamic response to kisspeptin-54 and pituitary response to GnRH, but impaired testicular response. Further work is required to investigate the use of kisspeptin-54 to identify hypothalamic deficits in men with LOH.
- Subjects
KISSPEPTIN neurons; GONADOTROPIN releasing hormone; TESTOSTERONE; PITUITARY hormone releasing factors; HEALTH of older men; KISSPEPTINS
- Publication
Neuroendocrinology, 2018, Vol 106, Issue 4, p401
- ISSN
0028-3835
- Publication type
Article
- DOI
10.1159/000488452