Hypothalamic-pituitary axis tool

Abstract

In order to fulfill their roles in neuroendocrine regulation, specific hypothalamic neurons are devoted to produce and deliver biologically active peptides to the pituitary gland. The biosynthesis and release of peptides are strictly controlled by afferents to these hypothalamic neurons. Cell-specific expression and biosynthetic regulation largely relies on transcription from the gene promoter for which the 5′-flanking regions of the peptidergic genes contain essential elements. Cell-specific transcription factors employ these regulatory elements to exert their control over the expression of the peptidergic gene. This article explores the properties of regulatory elements of the major hypothalamic peptides, somatostatin, growth hormone-releasing hormone, gonadotropin-releasing hormone, thyrotropin-releasing hormone, corticotropin-releasing hormone, vasopressin and oxytocin, and the transcription factors acting on them. These transcription factors are often endpoints of signal transduction pathways that can be activated by neurotransmitters or steroid hormones. Others are essential to provide cell-specific expression of the peptidergic gene during development and mature regulation.

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Section snippets

Introduction: Gene regulation, promoters, regulatory elements, and transcription factors

The peptides produced by hypothalamic neurons are the essential signaling molecules in neuroendocrine regulation. These peptidergic neurons form intrahypothalamic regulatory networks together with other transmitter systems, or provide directly hypothalamic “peptidergic output” in the control of pituitary activity and peripheral functions. Today over 50 genes are known that encode biologically active peptides, most of them expressed as “neuropeptide genes” in neuronal systems. Many are expressed

The somatostatin (ST) promoter

Somatostatin (ST) belongs to the first releasing factors discovered. Its inhibitory influence on the pituitary somatotrophes places ST in a key role in the neuroendocrine control of growth. Consequently, the expression of the ST gene has been focus of extensive molecular study. In addition to the hypothalamus, the ST gene is widely expressed in other neuronal and endocrine tissues, where it displays generally inhibitory endocrine or paracrine actions. In view of these divers functions, the ST

Concluding remarks

The transcriptional regulation of peptidergic genes and action of transcription factors are hard to study directly in hypothalamic neurons despite several innovative methodologies [16]. This is due to the small numbers and anatomical heterogeneity of neurons. For this reason, our knowledge on the transcriptional regulation of hypothalamic peptides lacks behind in comparison to other biological systems, e.g., the liver. Heterologous cell systems in vitro have only been of initial help to

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Cited by (35)

• Vasopressin and oxytocin release within the brain: A dynamic concept of multiple and variable modes of neuropeptide communication 2004, Frontiers in Neuroendocrinology Suckling, for example, evokes OXT release in the SON before significant peripheral secretion [179], whereas, after osmotic stimulation, dendritic OXT release lags behind peripheral secretion [155,198]. Neuropeptide gene expression regulated by gene promoters determines the amount of newly synthesized neuropeptide available for central release as well as peripheral secretion [27,40,186]. In addition to afferents to neurosecretory neurons, including local circuits proximal to the PVN [101–103,267], expression and synthesis are thus controlled by intrinsic, cell-autonomous mechanisms, particularly by the structure of the neuropeptide gene promoter itself and its interaction with transcription factors.