Intermediate lobe

Melatonin [73-31-4] C 2H N202 (31) has marked effects on circadian rhythm (11). Novel ligands for melatonin receptors such as (32) (12), C2yH2gN202, have affinities in the range of 10 Af, and have potential use as therapeutic agents in the treatment of the sleep disorders associated with jet lag. Such agents may also be usehil in the treatment of seasonal affective disorder (SAD), the depression associated with the winter months. Histamine (see Histamine and histamine antagonists), adenosine (see Nucleic acids), and neuropeptides such as corticotropin-like intermediate lobe peptide (CLIP) and vasoactive intestinal polypeptide (VIP) have also been reported to have sedative—hypnotic activities (7). 

In addition to the weU-defined opioid systems in the central nervous system, the three opioid peptides and their precursor mRNA have also been identified in peripheral tissues. ( -Endorphin is most abundant in the pituitary, where it exists in corticotroph cells with ACTH in the anterior lobe and in melanotroph cells with MSH in the intermediate lobe (59). Enkephalin and pre-pro-enkephalin mRNA have been identified in the adrenal medulla (60) and this has been the source of material for many studies of pro-enkephalin synthesis and regulation. Pre-pro-enkephalin mRNA has also been identified in the anterior and posterior lobes of the pituitary (61). mRNA for all three opioid precursors has been identified in the reproductive system (62—64). POMC... 

CLIP Corticotropin-hke intermediate lobe peptide OHSD Hydroxysteroid dehydrogenase PNMT Phenylethanolamine-W-methyltransferase ... 

The POMC gene is expressed in the anterior and intermediate lobes of the pituitary. The most conserved sequences between species are within the amino terminal fragment, the ACTH region, and the (3-endorphin region. POMC or related products are found in several other vertebrate tissues, including the brain, placenta, gastrointestinal tract, reproductive tract, lung, and lymphocytes. 

The POMC protein is processed differendy in the anterior lobe than in the intermediate lobe. The intermediate lobe of the pituitary is mdimentary in adult humans, but it is active in human fetuses and in pregnant women during late gestation and is also active in many animal species. Processing of the POMC protein in the peripheral tissues (gut, placenta, male reproductive tract) resem-... 

Figure 42-15. Products of pro-opiomelanocortin (POMQ cleavage. (MSH, melanocyte-stimulating hormone CLIP, corticotropin-like intermediate lobe peptide LPH, lipotropin.)...

FIGURE 18-7 Processing of the proopiomelanocortin (POMC) precursor proceeds in an ordered, stepwise fashion. Cleavage of the POMC precursor occurs at seven sites, with some of the reactions being tissue-specific. The circled numbers indicate the temporal order of cleavage in tissues where these proteolytic events occur. ACTH, adrenocorticotropic hormone CLIP, corticotropin-like intermediate lobe peptide JP, joining peptide LPH, lipotropin MSH, melanocyte-stimulating hormone PC, prohormone convertase. 

The intermediate length systems include the tuberoinfundibular system, which projects from the arcuate and periventricular nuclei into the intermediate lobe of the pituitary and the median eminence. This system is responsible for the regulation of such hormones as prolactin. The inter hypothalamic neurons send projections to the dorsal and posterior hypothalamus, the lateral septal nuclei and the medullary periventricular group, which are linked to the dorsal motor nucleus of the vagus such projections may play a role in the effects of dopamine on the autonomic nervous system. 

Following messenger formation, the amount and types of proteins can be modulated in additional ways. The initial polypeptide can be processed in various ways so that different polypeptides or proteins are expressed in different tissues. Such a situation exists for processing the precursor polypeptide preproopiomelanocortin (see fig. 24.7). This polypeptide is processed in different ways in the anterior and intermediate lobes of the pituitary gland to give rise to different hormones in these two tissues. 

The hypothalamic control of the posterior pituitary is quite different than that of the anterior and intermediate lobes. Specific neurons have their cell bodies in certain hypothalamic nuclei. Cell bodies in the paraventricular nuclei manufacture oxytocin, whereas the supraoptic nuclei contain cell bodies that synthesize ADH. The axons from these cells extend downward through the infundibulum to terminate in the posterior pituitary. Hormones synthesized in the hypothalamic cell bodies are transported down the axon to be stored in neurosecretory granules in their respective nerve terminals (located in the posterior pituitary). When an appropriate stimulus is present, these neurons fire an action potential, which causes the hormones to release from their pituitary nerve terminals. The hormones are ultimately picked up by the systemic circulation and transported to their target tissues. 

The D-2 Dopamine Receptor in the Intermediate Lobe of the Rat Pituitary Gland... 

Dopaminergic neurons synapse upon the parenchymal cells of the intermediate lobe (IL) of the rat pituitary gland. Dopamine decreases the capacity of the IL cells to synthesize cyclic AMP and inhibits the release of otMSH and other peptides from this tissue. The presence of a D-2 receptor accounts for both of these phenomena. This D-2 dopamine receptor can be studied in a binding assay using [3H]-spiroperidol, a dopamine... 

The dopamine receptor in the intermediate lobe of the pituitary gland is negatively coupled to adenylate cyclase... 

The above-described data show that CRF added to cells of the rat Intermediate lobe In culture causes a rapid stimulation of oe-MSH release and cyclic AMP accumulation, thus demonstrating a direct action of the peptide on pars intermedia cells (15). It is however difficult, using intact cells, to dissociate between increases in cyclic AMP levels due to stimulation of adenylate cyclase activity or to Inhibition of cyclic nucleotide phosphodiesterase or to a combination of both effects. Definitive proof of the role of adenylate cyclase In the action of CRF In the intermediate lobe of the pituitary gland is provided by the following findings of a CRF-lnduced stimulation of adenylate cyclase activity in homogenate of rat and bovine pars Intermedia cells. 

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