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It is now clearly established that the brain has the capability of synthesizing various biologically active steroids including 17-hydroxypregnenolone (17OH-Δ5P), 17-hydroxyprogesterone (17OH-P), dehydroepiandrosterone (DHEA) and androstenedione (Δ4). However, the presence, distribution and activity of cytochrome P450 17α-hydroxylase/C17, 20-lyase (P450C17), a key enzyme required for the conversion of pregnenolone (Δ5P) and progesterone (P) into these steroids, are poorly documented. Here, we show that P450C17-like immunoreactivity is widely distributed in the frog brain and pituitary. Prominent populations of P450C17-containing cells were observed in a number nuclei of the telencephalon, diencephalon, mesencephalon and metencephalon, as well as in the pars distalis and pars intermedia of the pituitary. In the brain, P450C17-like immunoreactivity was almost exclusively located in neurons. In several hypothalamic nuclei, P450C17-positive cell bodies also contained 3β-hydroxysteroid dehydrogenase-like immunoreactivity. Incubation of telencephalon, diencephalon, mesencephalon, metencephalon or pituitary explants with [3H]Δ5P resulted in the formation of several tritiated steroids including 17OH-Δ5P, 17OH-P, DHEA and Δ4. De novo synthesis of C21 17-hydroxysteroids and C19 ketosteroids was reduced in a concentration-dependent manner by ketoconazole, a P450C17 inhibitor. This is the first detailed immunohistochemical mapping of P450C17 in the brain and pituitary of any vertebrate. Altogether, the present data provide evidence that CNS neurons and pituitary cells can synthesize androgens. [ABSTRACT FROM AUTHOR]

26RFa is a novel RFamide peptide originally isolated in the amphibian brain. The 26RFa precursor has been subsequently characterized in various mammalian species but, until now, the anatomical distribution and the molecular forms of 26RFa produced in the CNS of mammals, in particular in human, are unknown. In the present study, we have investigated the localization and the biochemical characteristics of 26RFa-like immunoreactivity (LI) in two regions of the human CNS – the hypothalamus and the spinal cord. Immunohistochemical labeling using specific antibodies against human 26RFa and in situ hybridization histochemistry revealed that in the human hypothalamus 26RFa-expressing neurons are located in the paraventricular and ventromedial nuclei. In the spinal cord, 26RFa-expressing neurons were observed in the dorsal and lateral horns. Characterization of 26RFa-related peptides showed that two distinct molecular forms of 26RFa are present in the human hypothalamus and spinal cord, i.e. 26RFa and an N-terminally elongated form of 43 amino acids designated 43RFa. These data provide the first evidence that 26RFa and 43RFa are actually produced in the human CNS. The distribution of 26RF-LI suggests that 26RFa and/or 43RFa may modulate feeding, sexual behavior and transmission of nociceptive stimuli. [ABSTRACT FROM AUTHOR]

This study describes the expression of PAC1 and VPAC1 receptor (PAC1-R and VPAC1-R) mRNAs in the brain of frog ( Rana esculenta) during development. PAC1-R mRNA was detected in the periventricular and subependymal layers of the thalamus and epithalamus and in the ependymal layer of the mesencephalon and rhombencephalon (stage 20), in the amygdala, in the habenular complex, in the periventricular nucleus of the hypothalamus, and in the ventral cerebellum (stage 30). VPAC1-R mRNA expression was observed only at stage 20, in the floor of the hypothalamus. These results suggest that, in amphibians, pituitary adenylate cyclase-activating polypeptide (PACAP) may play a role in brain development. [ABSTRACT FROM AUTHOR]

In the present study, we report the identification, in the frog brain, of a novel neuropeptide, termed 26RFa, that belongs to the RFamide peptide family. The cDNAs encoding the precursors for 26RFa have been characterized in human and rats. In rats, prepro-26RFa mRNA is expressed exclusively in two hypothalamic nuclei involved in the control of feeding behavior. Intracerebroventricular injection of 26RFa in mice induced a dose-dependent increase in food consumption. Taken together, these data indicate that 26RFa is a novel neuropeptide that may have important biological functions in vertebrates. [ABSTRACT FROM AUTHOR]

A preface to the 2009 issue of "Annals of the New York Academy of Sciences" is presented.