Hybridization histochemical and immunohistochemical localization of inhibin/activin subunits and messenger ribonucleic acids in the rat brain

Abstract

Inhibin and activin are best known as gonadal glycoprotein hormones but have a broad anatomical distribution. We previously described the central distribution ofinhibin/activin beta A- and beta B-subunit proteins in some neuronal cell bodies, fibers, and nuclei of the rat brain and reported a possible role for central activin in suckling-induced oxytocin secretion and corticotropin releasing factor release. In the present report, we mapped the detailed immunohistochemical localization of inhibin/activin alpha-, beta A-, and beta B-subunits throughout the rat brain to further clarify their central distribution. In addition, the localization and distribution of their corresponding mRNAs was assessed. The results are summarized as follows: 1) Both beta A- and beta B-subunit immunoreactivity are found in neuronal cell bodies in the nucleus of the solitary tract and the dorsal and ventral medullary reticular nuclei, and in fibers and terminals of known projection sites for these nuclei. 2) beta B-subunit immunoreactivity is localized in a group of perifornical neurons in the hypothalamus. 3) beta A-subunit immunoreactivity is present in discrete populations of neuronal cell nuclei scattered throughout the CNS. 4) mRNAs encoding each of the inhibin/activin subunits are expressed in all major brain regions as determined by S1 nuclease assay and in a variety of specific neuroanatomical sites as shown by in situ hybridization. The results suggest that central inhibin and activin proteins are produced in the brain where they may potentially serve inter- and intracellular functions in multiple systems.

Activin A concentrations in human cerebrospinal fluid are age-dependent and elevated in meningitis

“…Follistatin (FS) is a high affinity binding protein of activin and antagonizes its actions [6][7][8]. Proteins and mRNA of activin and FS show a wide tissue distribution [9][10][11][12][13][14] and both are detected in the central nervous system (CNS, [15][16][17]). …”

Activin is a Neuronal Survival Factor that is Rapidly Increased after Transient Cerebral Ischemia and Hypoxia in Mice

“…Embryonic neurons are dependent on the continual presence of growth factors for their survival while adult neurons may require trophic support only in times of injury (Benn and Woolf, 2004). Activin mRNA and protein are present at basal levels throughout the adult brain including cortical regions (Roberts et al, 1996) with significant upregulation of activin mRNA, its protein and activin signals in adult neurons can be detected within hours after injury (our data; Tretter et al, 1996;Dow et al, 2005;Bottner et al, 2006). Because activin administration protects adult hippocampal neurons from excitotoxic kainic acid and quinolic acid addition in vivo Tretter et al, 2000), it seems likely that increased amounts will improve neuronal survival after ischemic injury.…”

Activin mRNA induced during amygdala kindling shows a spatiotemporal progression that tracks the spread of seizures

“…Two type II receptors, ActR-II and ActR-IIB, have been identified (Mathews and Vale, 1993). Expression of mRNA and protein for activin subunits (Roberts et al, 1996) and activin receptor types (Bengtsson et al, 1995;Cameron et al, 1994;Funaba et al, 1997;Morita et al, 1996;Soderstrom et al, 1996) has been demonstrated and partially mapped in the CNS. Both activin subunit mRNAs, ␤A and ␤B, are constitutively expressed in the CNS (Andreasson and Worley, 1995).…”