Small animals who have magically mutated into monstrously large proportions make for some of the best B-movies in science. Attack of the Killer Shrews and the Giant Gila Monster are some of my favorites. We know more or less that these things can’t really happen, but turns out, the physiological and genetic mechanisms behind how fast and big an animal grows are still a mystery. New experiments with fruit flies reveal how the interplay of three hormones regulates body size.
Two mechanisms determine how big an animal gets: One controls growth rate, the other controls growth duration. The first commands how fast an animal grows and depends on insulin and similar hormones that prompt cells to divide and multiply. The latter regulates the timing of maturation using developmental hormones (like androgens and estrogens in people). A team led by Christen Mirth from Instituto Gulbenkian de Ciência and Alexander Shingleton of Lake Forest College investigated the two largely independent processes in Drosophila fruit flies.
In these insects, growth rates are regulated by the insulin-signaling pathway. Two other hormones regulate developmental transitions and growth duration -- which in the flies' case includes metamorphosis, from larvae to flies. One of these hormones is called ecdysone (“the molting hormone”), and elevated levels prompt insects to undergo changes like shedding old skin. The other is called juvenile hormone (JH), and a low level of this stops growth and initiates metamorphosis. Previous studies have shown that bug size can be manipulated (to some extent) by fiddling with these hormonal pathways.
The new findings reveal an intimate link between the three: Juvenile hormone controls body size by regulating ecdysone synthesis, which in turn modifies insulin signaling.
The researchers bred JH-deficient flies (who can’t produce the growth-stopping JH), and then compared their growth timing and hormone levels to normal flies. They found that JH-deficient flies were stunted but not because they didn’t metamorphose prematurely: Loss of JH slowed the rate of growth without changing the timing of metamorphosis.
Altering a JH-deficient fly’s ability to produce the other two growth-related hormones can eliminate the stunting effect. If ecdysone levels were boosted, or if researchers could prevent the molting hormone from turning off insulin production, a JH-deficient fly could still grow to a normal size.
This extensive crosstalk between the hormones was surprising, Mirth tells Science. “JH acts to fine-tune growth rates” by influencing the effects of the other two hormones, she adds.
The work was publishing in Proceedings of the National Academy of Sciences last week.