Growth and reproduction are intimately linked by the endocrine system. Pituitary growth hormone (GH) is a major driver of body growth, and modulation of its expression and secretion can be influenced by sex hormones. Despite the established relationship between growth and reproduction, however, the precise role of the gonads in regulating body growth has not been adequately studied, particularly in species displaying sexual growth differences.
Takeshi Miura and his team from Ehime University in Japan began their study with a simple question – what role do the gonads play in body growth? To answer this question, they removed the gonads from Mozambique tilapia (Oreochromis mossambicus) 40 days after hatching – when the immature fish can be readily sexed by eye. Then, some fish received their gonads back, although the scientists relocated the gonads between the skin and muscle, and all the fish were weighed 50 days later (at sexual maturity) to determine whether there were any differences in their body masses. Miura and colleagues also measured plasma concentrations of key sex hormones – including 11-ketotestosterone, which is usually produced by the testes and estradiol, which is usually produced by the ovaries – as well as plasma growth hormone and gene expression levels of growth hormone and insulin-like growth factor 1.
The researchers found that fish of both sexes without gonads had significantly reduced body mass compared with fish that had not had their gonads removed. In addition, the fish that had regained their gonads after they were initially removed fully recovered their mass. However, when the team looked at the fish's sex hormone levels (11-ketotestosterone and estradiol) there was no correlation between sex hormone level and body size, with males and females showing different hormone patterns. Therefore, as the growth patterns of the two sexes responded identically to the loss and return of their gonads, the changes between the sexes indicate that sex hormones alone cannot explain the influence of gonads on growth.
The authors then looked to growth hormone and insulin-like growth factor 1 to explain how gonads directly influence growth. While there were no differences between treatments in the transcript levels of these genes in the pituitary, gonads or liver, levels of growth hormone in the plasma were significantly reduced in male and female tilapia that had lost their gonads. However, the males and females that had received their gonads back fully recovered their plasma growth hormone levels, suggesting that growth hormone produced by the gonads is secreted into the blood to help regulate body growth. This finding is particularly important as it calls into question the long-held assumption that all circulating growth hormone originates from the pituitary. While many other tissues express growth hormone, the conventional thought is that it acts locally and is not secreted into the blood. Miura's study suggests that the gonads are also significant sources of circulating growth hormone, at least in teleosts.
Using a conceptually simple technique, Miura's team clearly show that fish gonads are necessary for normal growth in teleosts, and that growth hormone – not sex steroids – is the major factor governing this relationship. Another important finding is that the pituitary may not be the sole source of circulating growth hormone in non-mammalian vertebrates, opening new avenues of research into the functions of growth hormone from tissues other than the pituitary.