Anti-Müllerian hormone may regulate the number of calbindin-positive neurons in the sexually dimorphic nucleus of the preoptic area of male mice

BACKGROUND: The male brain is putatively organised early in development by testosterone, with the sexually dimorphic nucleus of the medial preoptic area (SDN) a main exemplifier of this. However, pubescent neurogenesis occurs in the rat SDN, and the immature testes secrete anti-Müllerian hormone (AMH) as well as testosterone. We have therefore re-examined the development of the murine SDN to determine whether it is influenced by AMH and/or whether the number of calbindin-positive (calbindin(+ve)) neurons in it changes after pre-pubescent development. METHODS: In mice, the SDN nucleus is defined by calbindin(+ve) neurons (CALB-SDN). The number and size of the neurons in the CALB-SDN of male and female AMH null mutant (Amh(-/-)) mice and their wild-type littermates (Amh(+/+)) were studied using stereological techniques. Groups of mice were examined immediately before the onset of puberty (20 days postnatal) and at adulthood (129–147 days old). RESULTS: The wild-type pre-pubertal male mice had 47% more calbindin(+ve) neurons in the CALB-SDN than their female wild-type littermates. This sex difference was entirely absent in Amh(-/-) mice. In adults, the extent of sexual dimorphism almost doubled due to a net reduction in the number and size of calbindin(+ve) neurons in females and a net increase in neuron number in males. These changes occurred to a similar extent in the Amh(-/-) and Amh(+/+) mice. Consequently, the number of calbindin(+ve) neurons in Amh(-/-) adult male mice was intermediate between Amh(+/+) males and Amh(+/+) females. The sex difference in the size of the neurons was predominantly generated by a female-specific atrophy after 20 days, independent of AMH. CONCLUSIONS: The establishment of dimorphic cell number in the CALB-SDN of mice is biphasic, with each phase being subject to different regulation. The second phase of dimorphism is not dependent on the first phase having occurred as it was present in the Amh(-/-) male mice that have female-like numbers of calbindin(+ve) neurons at 20 days. These observations extend emerging evidence that the organisation of highly dimorphic neuronal networks changes during puberty or afterwards. They also raise the possibility that cellular events attributed to the imprinting effects of testosterone are mediated by AMH.