5.2 Sexually dimorphic nucleus of the preoptic area (SDN-POA)
As well as affecting behaviour (Section 3.4) neonatal testosterone also affects the physical characteristics of some areas of the brain. One of these is a small area of the hypothalamus, the medial preoptic area, which, although small, is much larger in males than in females. This size difference is mediated by testosterone.
There is a group, a nucleus, of neurons in the medial preoptic area of both male and female prenatal rats where the neuronal cell bodies are clustered together at an unusually high density. By about the first or second day after birth, the volume of this high-density nucleus is larger in male rats than in female rats, a difference that persists into adulthood. The density of neurons in this nucleus is the same in both males and females; it is its volume that is different. The high-density area is known as the sexually dimorphic nucleus of the preoptic area, SDN-POA. The difference in size comes about through the action of testosterone on the developing brain.
The effects on the volume of the SDN-POA of a single injection of testosterone into neonatal female rats and of castration of neonatal male rats are shown in Figure 11. Note the injection consisted of testosterone mixed with oil, not water or saline solution.
In Figure 11 the SDN-POA volume is expressed as a percentage of the volume of this nucleus in control male rats, 30 days after treatment. Normal female rats are shown in A and normal males in B. In C, males were castrated on postnatal day 1 (C–P1) and given an injection of oil on postnatal day 2 (oil–P2); in D, similar males (C–P1) were also injected with testosterone on day 2 (T–P2). In E, females were injected with testosterone on postnatal day 4 (T–P4).
What effect did the neonatal testosterone injection have on the size of the SDN-POA in the females? (E in Figure 11.)
Answer
The single injection of testosterone into neonatal female rats more than doubled the size of the nucleus compared with normal females, to a size almost half that seen in normal males.
The results from these experiments suggest that the volume of the nucleus is affected by testosterone, but some of the differences still need to be accounted for.
What differences still need to be accounted for?
Answer
The volume of the nucleus in castrated males is greater than that of normal females (Figure 11 treatment group C compared with group A) and its volume in females treated with testosterone is not as great as that of normal males (treatment group E compared with group B).
In spite of these differences, it could still be claimed that testosterone can account for all of the observed SDN-POA volume differences between males and females. Explain how this is possible.
Answer
It would be possible if testosterone exerts some of its effects prenatally. Then these prenatal effects would be missing from the experiments, where all the manipulations were carried out postnatally.
In fact a more prolonged exposure to testosterone, beginning prenatally, does result in female rats with an SDN-POA volume equivalent to that of normal males.
The presence or absence of testosterone during the neonatal period alters the size of the SDN-POA. However, the question of how testosterone exerts its effects remains unanswered. There are essentially two separate problems:
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How does testosterone alter the volume of neurons in the preoptic area?
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How does a change in volume of neurons in the preoptic area affect behaviour?
The first question can be answered by considering what testosterone does inside the cell. Testosterone is a steroid hormone, which is important only insofar as steroid hormones can pass straight through cell membranes: no special receptors or transport mechanisms are needed. There are however, special receptors for steroid hormones inside cells. Once inside the neurons of the SDN-POA, testosterone is converted into oestradiol. (Note: This may seem perverse, given that oestradiol is one of the main hormones secreted by the mature ovary, and is often characterised as a female hormone. However, the immature ovary, e.g. the ovary of the neonatal female rat, produces very little oestradiol, and what is produced is mopped up by another molecule, alphafetoprotein.)
The oestradiol combines with its receptor, and the combined molecule then interacts with the DNA to produce new proteins. One of the new proteins produced under these circumstances is thought to be what is known as a survival molecule (BDNF) which protects the cell from cell death. Survival molecules are considered further in Section 7.
In summary then, testosterone protects the neurons in the SDN-POA from dying.
Activity 11
Does this provide an answer to second question in Activity 10?
Answer
Yes it does. Neurons in the SDN-POA of males are protected and survive, whereas neurons in the SDN-POA of females are not protected and die resulting in a smaller SDN-POA in females.
Question 2 is a little bit more tricky and at present very little can be said about the link between the size of the SDN-POA and behaviour, but two things are clear. The SDN-POA is not part of the sensory pathways to the brain, and neither is it part of the motor pathways from the brain. The differences in size of the SDN-POA must alter, in some way, how information is processed within the brain. The road to resolving this cause-effect relationship still snakes off some way into the distance.