Intermediate lobe hormones

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 direct actions of DA on pituitary hormone secretion are largely inhibitory, maintaining basal secretion of prolactin from anterior pituitary lactotrophs and POMC-derived peptide hormones from intermediate lobe melanotrophs via inhibitory D2 receptors located on these cells. Episodic surges of these hormones are associated with... 

In summary, during periods of some forms of stress TIDA and PHDA neurons receive a convergence of inhibitory inputs mediated, at least in part, by opioid, cholinergic, histaminergic, serotoninergic and GABAergic neurons. The inhibition of TIDA neurons (in female rats) and PHDA neurons (in both sexes) culminates in hormonal responses the release of prolactin from lactotrophs in the anterior lobe of the pituitary and of aMSH from melanotrophs in the intermediate lobe of the pituitary. 

Von Euler G, Meister B, Hokfelt T, Eneroth P, Fuxe K (1990) Intraventricular injection of neurotensin reduces dopamine D2 agonist binding in rat forebrain and intermediate lobe of the pituitary gland. Relationship to serum hormone levels and nerve terminal coexistence. Brain Res 537 253-262. 

MSHs consist of three peptide hormones a-MSH, 3-MSH, and y-MSH, which are secreted by intermediate lobe of the pituitary gland. They are cleaved from the same precursor peptide as ACTH. Their basic function is stimulation of melanocytes to darken skin and stimulation of melanin synthesis to darken the skin and hair. They also have been found to be released in the brain affecting appetite, sexual arousal, and many other functions. 

Some polyproteins are differentially cleaved in different tissues. An example is proopiomelanocortin, a polyprotein that is the source of several hormones synthesized in the pituitary gland. In the anterior lobe of the pituitary, the polyprotein is cleaved to release -lipotropin and adrenocorticotropic hormone (ACTH). In the intermediate lobe, a different pattern of cleavage forms jS-endorphin and a-melanotropin (Chapter 31). 

PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH, corticotropin), and j6-endorphin. /6-Lipotrophic hormone (/1-LPH) is also secreted but serves mainly as a precursor of -endorphin and is not regarded as a hormone. In species that possess a prominent intermediate lobe, the pituitary also secretes a-and /i-melanocyte-stimulating hormones (MSH), which affect skin coloration. 

Fig. 1. Processing of proopiomelanocortin (POMC) the precursor for the melanocortins and opiates in the mammalian pituitary gland. Processing occurs by proteolytic cleavage at sites of paired amino acids, some of which are shown here as dark bands. In both the anterior and the intermediate lobes, POMC is processed into an ACTH biosynthetic intermediate and into )J-lipotropin ()3-LPH 1-91). In the anterior lobe, subsequent processing yields the two biologically important products, ACTH 1-39 and )S-MSH. In the intermediate lobe, ACTH 1-39 is further processed to yield a-MSH (ACTH 1-13) and corticotropin-like intermediate peptide (CLIP). -MSH is derived, via y-MSH, from the 16-K fragment of POMC. This hormone varies in length in different species. Also in the intermediate lobe, /3-LPH is processed to produce p-endorphin 1-31. Many other small peptide fragments, of uncertain biological properties, are also produced, (from Strand et al., 1989).

Lipotropin, lipotropic hormone, LPH, a polypeptide hormone from the hypophysis stimulating the mobilization of lipids from lipid depots. fi-LPH (91 aa Mr 10 kDa) is biosyntheticaUy formed from the precursor proopiomelanocortin (PMOC). S-LPH is released from PMOC in the anterior and intermediate lobes of the pituitary gland, whereas in the intermediate lobe only fi-LPH is split to y-LPH (corresponds to fi-LPH 1-58) and -endorphin [A. F. Bradbury et al., Biochem. Biophys. Res. Commun. 1976, 69,950 J. Bogard et al.,/. Biol. Chem. 1995, 270, 23038]. 

Connected to the brain by a stalk (Fig. 30-1), the pituitary gland releases at least ten peptide or protein hormones that regulate the activity of other endocrine (hormone-producing) glands in distant parts of the body. The pituitary is composed of several distinct parts the anterior lobe (adenohypophysis), a thin intermediate portion (pars intermedia), and a posterior lobe (neurohypophysis). Each has its own characteristic endocrine functions. 

Effect of HA on hormone secretion from rat anterior, intermediate and posterior pituitary lobes... 

Dopamine can thus be added to the list of hormones and neurotransmitters which can stimulate or inhibit cyclic AMP formation, depending upon their tissue of action. Thus, while dopamine stimulates cyclic AMP formation in parathyroid cells, superior cervical ganglia, retina and striatal tissue (27, 58-61), it inhibits the accumulation of the cyclic nucleotide in cells of the intermediate and anterior lobes of the pituitary gland. Opposite effects on the cyclic AMP system are also found with LHRH which stimulates and inhibits cyclic AMP levels in the anterior pituitary gland (62) and ovary (63), respectively. Similarly, alpha-adrenergic agents show opposite effects on cyclic AMP formation in brain (64) and platelets (65). PGE, stimulates cyclic AMP formation in the anterior pituitary gland (62) while it inhibits the same parameter in fat cells (66). 

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