Naked mole-rats are fascinating little creatures. They live in large social colonies underground, where they eat tubers, dig tunnels, defend their colony from predators and reproduce. That last one, however, is usually restricted to just the dominant female of the colony (the queen) and a dominant male. This means that the vast majority of the colony, including all the subordinate females, do not produce offspring. Physiologically, these females are unable to have young because their fertility is reduced – meaning that the hormonal signalling pathway from their brain to their ovaries is apparently suppressed. However, this suppression seems to be alleviated when the subordinate females are taken away from their colony: within a week, their fertility is restored and they are able to reproduce once again. To figure out what mechanism is behind this suppression of reproduction in the subordinate females, Daniel Hart, Erin Roberts and colleagues at the Universities of Pretoria and Cape Town in South Africa took a closer look at the physiology of the females in their naked mole-rat colonies.

An important player in the hormonal signalling pathway needed for reproduction is luteinizing hormone, which tends to be lower in subordinate naked mole-rats compared with the queens. Luteinizing hormone is produced by the pituitary gland, just beneath the brain, and signals to the ovaries to make the changes required for reproduction. When these changes are complete, the ovaries signal back to the brain and pituitary to say, ‘that's enough’, and they respond by shutting down luteinizing hormone production in a process called negative feedback. The researchers thought that negative feedback may be overactive in subordinates, leading to lower luteinizing hormone and reproductive dysfunction. To test this, they surgically removed the ovaries of queens and subordinate females to remove these negative feedback signals and measured the luteinizing hormone levels in the animals’ blood, expecting a greater luteinizing hormone rise in subordinates than in queens. However, luteinizing hormone levels rose similarly in both, so this probably wasn't the fertility-suppressing culprit.

Next, they turned their attention to their second suspect in the search for the reproductive disruptor: the stress response. Why? Because the queen is a bit of a bully, with a tendency to shove and even bite her subordinates. When animals experience a stressful situation, they produce the hormone cortisol to help them cope and, in some species, cortisol can reduce fertility. They measured cortisol in the blood of queens and subordinate females and found, unexpectedly, that the stress hormone was lower in the blood of the subordinates. Given cortisol levels were not high in the subordinates, this stress hormone was probably not the culprit either.

When stressed, animals can produce their own pain relievers, called endogenous opioid peptides. These internally produced pain relievers can interfere with fertility and so were suspect number three. Using a drug called naloxone, Hart, Roberts and colleagues blocked the ability of these pain relievers to work and then measured the animals’ luteinizing hormone levels, expecting the blockade of internally produced pain relievers to enhance the rise in hormone levels. Instead, they saw the opposite: luteinizing hormone barely rose when the subordinate naked mole-rat females were treated with naloxone, suggesting that endogenous opioid peptide pain relievers aren't interfering with the subordinate naked mole-rats’ fertility.

It seems that feedback signals from the ovaries that reduce luteinizing hormone levels, stress and internally produced pain relievers are not responsible for the suppression of the subordinate naked mole-rats’ fertility. Now that the researchers have ruled out these major suspects, they've set their sights on some new suspects for investigation, including the multifunctional hormone prolactin. So, the curious case of how these social, subterranean, sparsely haired rodents regulate their reproduction based on rank remains to be unravelled.

Hart
,
D. W.
,
Roberts
,
E.
,
O'Riain
,
M. J.
,
Millar
,
R. P.
and
Bennett
,
N. C.
(
2024
).
The curious case of the hypothalamic–pituitary–gonadal axis dysfunction in subordinate female naked mole-rats (Heterocephalus glaber): no apparent role of opioids and glucocorticoids
.
J. Neuroendocr
.
36
,
e13444
.