Sex differences in expression of serotonin receptors (subtypes 1A and 2A) in rat brain: a possible role of testosterone

doi:10.1016/S0306-4522(99)00234-1

Neuroscience

Volume 94, Issue 1, September 1999, Pages 251-259

https://doi.org/10.1016/S0306-4522(99)00234-1 Get rights and content

Abstract

Sexual differences in the expression of messenger RNA and in the binding of serotonin receptors (subtypes 1A and 2A) were studied by in situ hybridization and autoradiography {[³H]8-hydroxy-2(di-n-propylamino)tetralin and [³H]ketanserin binding} in the rat brain. Serotonin-1A receptor messenger RNA showed distinct expression patterns for female and male rats. Expression of serotonin-1A receptor messenger RNA was greater in males in subregions of the hypothalamus and amygdala, and less in males in subregions of the hippocampus. No significant differences in the distribution of serotonin-1A receptor binding sites were found between the sexes. Serotonin-2A receptor messenger RNA expression was comparable in males and females in all brain regions except the ventromedial hypothalamic nuclei, where lower levels were seen in females. However, the binding of serotonin-2A receptor measured with [³H]ketanserin was significantly higher in females in all regions of the hippocampus. In a separate study, gonadectomy in males significantly increased serotonin-1A messenger RNA content in the cortex, hypothalamus, hippocampus, amygdala and dorsal raphe, and decreased serotonin-2A messenger RNA in ventromedial hypothalamic nuclei only. Almost all gonadectomy-induced changes were reversed by concomitant administration of testosterone.

Our data provide evidence for region-specific sex differences in serotonin receptor subtype 1A and 2A transcription and concentration in the rat brain, and further suggest a modulatory role of testosterone in serotonin (particularly subtype 1A) receptor expression. Gender and gonadal steroid effects on central serotonergic systems may underlie the reported sexual dimorphisms in affective state regulation, response to psychopharmacological agonists or pituitary adrenal activation.

Section snippets

Experimental procedures

These studies were conducted in an AALAC approved laboratory in accordance with NIH protocol no. 999 and in such a way as to minimize both animal suffering and the numbers of animals required.

Serotonin-1A receptor transcripts

In situ hybridization revealed that 5-HT_1A receptor mRNAs were expressed distinctly in male and female rats in the hippocampus (Fig. 1), as well as in the hypothalamus and amygdala. Compared to the relatively low levels of expression of 5-HT_1A message transcripts in cells of the CA3 and CA4 subfields evident in autoradiograms of the male hippocampus, there was relatively robust expression in these regions in the female hippocampus. Consistent with the literature,⁴⁰ the most intense labeling by

Role of testosterone in serotonin receptor subtype dimorphisms

We have identified sex-related differences in the distribution of 5-HT_1A mRNA and 5-HT_2A binding in juvenile rat brain. The distribution of 5-HT_1A and 5-HT_2A mRNAs and receptor binding sites that we observed conforms fairly well with prior investigations in adult male rats, demonstrating high binding in the hippocampus, raphe nuclei and cerebral cortex.10., 31., 40. The dimorphisms observed were 5-HT receptor subtype specific and brain region specific. 5-HT_1A mRNA was significantly higher in

Conclusions

We have shown the presence of sexual dimorphisms in 5-HT_1A receptor mRNA levels (hippocampus, hypothalamus, amygdala, dorsal raphe nucleus), 5-HT₂ mRNA (hypothalamus) and 5-HT_2A receptor binding (hippocampus). Additionally, we have demonstrated testosterone-dependent transcriptional regulation of 5-HT_1A and, to a lesser extent, 5-HT_2A receptors. The effect of these sexual dimorphisms on local patterns of electrical activity, systemic physiological response or subsequent brain development is

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Sex differences in expression of serotonin receptors (subtypes 1A and 2A) in rat brain: a possible role of testosterone

Abstract

Section snippets

Experimental procedures

Serotonin-1A receptor transcripts

Role of testosterone in serotonin receptor subtype dimorphisms

Conclusions

Brain Res.

Neurosci. Lett.

Prog. Neuropsychopharmac. biol. Psychiat.

Brain Res.

Neuroscience

Life Sci.

Brain Res.

Cell

Eur. J. Pharmac.

Brain Res. Bull.

Eur. J. Pharmac.

Physiol. Behav.

J. biol. Chem.

Physiol. Behav.

Neurochem. Int.

Neurosci. Res.

Physiol. Behav.

Brain Res.

Neuroscience

Eur. J. Pharmac.

Devl Brain Res.

Brain Res.

Molec. cell. Neurosci.

J. Steroid Biochem. molec. Biol.

Life Sci.

“Serotonin depression”—a biochemical subgroup within the affective disorders?

Science