The Role of Catecholaminergic and Serotoninergic Systems in Sexual Differentiation of the Mammalian Brain

Siddiqui, Arif (1986) The Role of Catecholaminergic and Serotoninergic Systems in Sexual Differentiation of the Mammalian Brain. PhD thesis, University of Glasgow.

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The neurotransmitters have an organizational role in the sexual differentiation of the mammalian brain. In rodents sex differences in brain amine concentrations appear to be dependent upon the levels of androgens circulating during the perinatal period. To examine the role of biogenic amines in sexual differentiation of the brain, newborn male rats were castrated, or sham-operated upon within 2k hours of birth. Newborn female rats received either 5 daily sc injections of 100 ug testosterone (in oil) or were administered oil vehicle only. Groups of animals were decapitated at the following assigned ages, 12, 60, 75, 90, 120 and 180 days. The brains were removed and separated into hypothalamus, amygdala, cerebral cortex, cerebellum, corpus callosum, hippocampus, corpus striatum and corpora quadrigemina. Circulating LH concentrations were measured by radioimmunoassay from blood samples collected from the above animals. Monoamine levels in each region of the brain were determined by high performance liquid chromatography coupled with electrochemical detection. Between 12 and 60 days, the biogenic amine content in almost all the brain regions increased more in control males and androgenised females than in control females and castrated males. Between 60 and 180 days there were variations with no clear pattern; at 180 days the amine contents were similar in control females and castrated males, and higher than those in control males and androgenised females, which were also similar to each other. Neonatal castration of male rats resulted in a significant depletion of the brain catecholaminergic content in the younger animals, after which a pronounced rise occurred by four to six months of age. This observation was generally true for all the regions examined. The rise in catecholamine content in the androgenized females observed at 60 days of age was however short-lived, and a gradual diminution then followed which continued through to 180 days of age. The brain 5-HT and 5-HIAA content of the neonatally castrated males was also reduced in the younger animals. However the situation was completely reversed by the time these rats reached 120-180 days of age. The 5-HT and 5-HIAA brain content of the androgenized females was higher than that of the controls at 60 days, but in the older experimental females the 5-HT content was greatly reduced compared to that of the oil-treated animals. These marked alterations in the central neurotransmitter systems are the results of a long-lasting generalized effect on the cell bodies of different neuronal groups. These modifications of the development of the brain biogenic amine systems may be a result of changes not only in mechanisms regulating the hypothalamic-pituitary-gonadal axis, but also of changes in certain non-reproductive functions sensitive to the neonatal androgen environment. An attempt was made to investigate the sex differences in the biogenic amine content of the hypothalamus, cerebral cortex and cerebellum of 17 human fetal brains obtained from prostaglandin-terminated mid-term pregnancies. There was a considerable variation in the amine levels of the tissues obtained from this source. This finding prompted a study of the post-mortem stability of monoamines in the rat brain and also an investigation of the effect of prostaglandins on neurotransmitter levels in fetal rabbit brain tissue. The stability of the monoamines varied differentially in various regions of the brain, leading to the suggestion that a correction factor be used to compensate for the changes seen. The experiments on the fetal rabbit brains confirmed that tissue obtained from prostaglandin-terminated pregnancies is not an ideal source for studying the androgen-dependent sex differences in the biogenic amine concentrations. This is because the prostaglandin itself interferes with the detection of the neurotransmitters. In the present study the results obtained are discussed in the light of previous work.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Medicine, Physiology, Neurosciences
Date of Award: 1986
Depositing User: Enlighten Team
Unique ID: glathesis:1986-77396
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 09:09
Last Modified: 14 Jan 2020 09:09

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