Rats with physically disconnected hypothalamo-pituitary tracts no longer contain vasopressin-oxytocin gene transcripts in the posterior pituitary lobe

AbstractIn rats, vasopressin- and oxytocin-encoding mRNAs are present in the posterior but absent in the anterior lobe of the pituitary gland. RNase protection experiments indicate that in the posterior pituitary and hypothalamus identical transcriptional start points are used. Furthermore, the two transcripts from posterior pituitary and hypothalamus show identical nucleotide sequences. Animals operated by paired electrical lesions in such a way that connections between the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus and the posterior pituitary lobeare destroyed continue to express the vasopressin and oxytocin gene in the hypothalamus but not in the posterior pituitary. Operated animals subjected to chronic intermittent salt loading for 6 days similarly contain vasopressin and oxytocin encoding transcripts in the hypothalamus but not in the posterior pituitary

Effect of hypoosmolality on the abundance, poly(A) tail length and axonal targeting of arginine vasopressin and oxytocin mRNAs in rat hypothalamic magnocellular neurons

AbstractArginine vasopressin (AVP) and oxytocin (OT) mRNAs are targeted to the axonal compartment of rat hypothalamic magnocellular neurons. Salt-loading results in a considerable rise in hypothalamic and axonal AVP mRNA but only a moderate increase for axonal OT mRNA. Here we report that hypoosmolality gives rise to a rapid decrease of axonal AVP encoding transcripts to undetectable levels after 2 weeks. The levels of OT mRNA in the axonal compartment did not change significantly. In the hypothalamus the mRNA for AVP also decreased. The size of the poly(A) tract of AVP encoding transcripts appeared to be strictly correlated with plasma osmolality. In contrast, the amount and size of OT encoding mRNAs were only moderately or not influenced by hypoosmolar stimuli

Expression of the vasopressin and oxytocin genes in human hypothalami

AbstractPoly(A)+ RNA isolated from post-mortem human hypothalami has been used to characterize the polyprotein precursors to vasopressin and oxytocin. Translation in a cell-free system and subsequent immunoprecipitation with antibodies raised against either vasopressin or neurophysin identified a product of Mr 19000 (prepro-vasopressin). A second less intense product of Mr 16500 was tentatively identified as prepro-oxytocin. A cDNA library derived from the human hypothalamic poly(A)+ RNA was screened for vasopressin and oxytocin-encoding cDNA using heterologous probes; clones encoding the two precursors were identified and found to be organized as their rat and bovine counterparts. Northern blot analysis shows that the mRNAs for the two prepro-hormones consist of ~ 840 (AVP) and ~ 700 (OT) nucleotides

Expression of the vasopressin and oxytocin genes in rats occurs in mutually exclusive sets of hypothalamic neurons

AbstractThe genes for the hypothalamic hormones vasopressin and oxytocin are located in close proximity to each other within the rat genome. They are separated by only approx. 11 kbp of DNA sequence and oriented in such a way that their transcription occurs on opposite DNA strands. Although the two genes are structurally very similar including common potential regulatory elements in their putative promotor regions, they are expressed in discrete populations of magnocellular neurons of the hypothalamus. In rats placed under osmotic stress, the vasopressin gene is unregulated; concomitantly transcription of the oxytocin gene is also stimulated. To address the question of whether this coordinated rise in oxytocin-encoding mRNA is the result of switching on oxytocin gene transcription in vasopressinergic neurons, in situ hybridization with double labelled cRNA probes was carried out. Biotinylated and [α-35S]CTP labelled antisense cRNA probes specific for either vasopressin or oxytocin mRNA were constructed and hybridized to hypothalamic sections from salt-loaded rats. The results demonstrate that upregulation of oxytocin gene transcription is restricted solely to oxytocinergic cells; no oxytocin gene transcripts can be detected in vasopressinergic neurons

The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP

Strong evidence indicates that regulated mRNA translation in neuronal dendrites underlies synaptic plasticity and brain development. The fragile X mental retardation protein (FMRP) is involved in this process; here, we show that it acts by inhibiting translation initiation. A binding partner of FMRP, CYFIP1/Sra1, directly binds the translation initiation factor eIF4E through a domain that is structurally related to those present in 4E-BP translational inhibitors. Brain cytoplasmic RNA 1 (BC1), another FMRP binding partner, increases the affinity of FMRP for the CYFIP1-eIF4E complex in the brain. Levels of proteins encoded by known FMRP target mRNAs are increased upon reduction of CYFIP1 in neurons. Translational repression is regulated in an activity-dependent manner because BDNF or DHPG stimulation of neurons causes CYFIP1 to dissociate from eIF4E at synapses, thereby resulting in protein synthesis. Thus, the translational repression activity of FMRP in the brain is mediated, at least in part, by CYFIP1.status: publishe