Prolactin

The release of prolactin from the adenohypophysis is a centrally mediated event involving the dopaminergic neurons. Stimulation of these neurons blocks prolactin production, whereas blockade of dopaminergic function causes lactation. Chlorpromazine, which blocks dopamine receptors  

This discussion clearly demonstrates that drugs do not create functions, but merely stimulate or inhibit functions already inherent in cells. These pharmacodynamic-related interactions occur at various levels of cellular activity, including ion transport, enzymes, coenzymes, nucleic acids, and numerous other biochemical events yet to be delineated. 

The primary function of TIDA neurons in both the females and males is to suppress the secretion of prolactin from the anterior pituitary. Indeed, experimental procedures that  

The regulation of vasopressin secretion by DA is multifaceted, likely involving participation of one or more separate populations of DA neurons under different physiological situations. Although the possibility exists that extrahypothalamic DA neurons may be involved in reflex activation of vasopressin release (Cornish et al., 1997), 

There is also experimental evidence that central DA neurons may be involved in inhibiting activated vasopressin secretion. In normal hydrated rats icv administration of DA suppresses anesthesia-induced vasopressin secretion (Forsling and Williams, 1984). Conversely, icv injection of a DA antagonist enhances vasopressin secretion in response to hemorrhage (Yamaguchi et al., 1990). No information is availability, however, regarding the identity of diencephalic neurons mediating the suppressive effects of DA on stimulated vasopressin release. 

On the basis of the results of early pharmacological studies it is generally believed that DA stimulates spontaneous release of oxytocin and facilitates suckling-induced reflex 

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Mechanism of Action. Eew data are available that describe the effects of anaboHc steroids on protein metaboHsm even fewer data exist for assessment of direct effects of anaboHc steroids on Hpid metaboHsm in growing mminants. The lack of any consistent change in somatotropin, prolactin, insulin, or other metaboHc hormones (qv) in a total of 15 studies has been noted (1,38). 

The primary stmcture of prolactin consists of 199 amino acids in a linear sequence (see Hormones, ANTERIORPITUITARY-LIKE HORMONES). Similar to growth hormone (16), the tertiary stmcture of prolactin is thought to be arranged in a bundle of four a-heHces (17). Detailed reviews of the... 

Structure—function relationships of prolactin among a variety of species have been pubUshed (17,18). Only one gene for prolactin appears to exist (19). Although classically placed in the category of simple protein hormones, prolactin can be glycosylated. Carbohydrate attachment occurs at Asn-31, where the consensus glycosylation sequence Asn—X—Ser is found. 

Chorionic Somatomammotropin. Three genes encode human chorionic somatomammotropin [11085-36-2] (hCS). These are located within a cluster of genes on human chromosome 17 which code for pituitary growth hormone [12629-01 -5] (GH-N), placental GH [109675-94-7J (GH-V), and three hCS molecules, ie, hCS-A, hCS-B, and hCS-V (1 3), also referred to as human placental lactogens. All of these molecules ate closely related to GH in stmcture (Fig. 1). Placental lactogens also exist in rodents and mminants however, these hormones are more closely related to prolactin than GH. 

Prolactin-Like Proteins. A number of prolactin-like proteins (PLPs), which ate distinct from the PLs, have been identified in mminants and rodents (11,23). Several cDNA transcripts coding for PLPs in catde have been identified (23). These transcripts code for proteins which possess about 40% sequence homology with bovine PRL 60% if conservative substitutions ate considered. Three glycosylated PLPs, ie, PLP-A, -B, and -C, ate produced during pregnancy in the rat (11). Two additional prolactin-related molecules have been identified in the mouse (24,25), ie, proliferin [92769-12-5] (PLF) and PLF-related protein [98724-27-7]. These ate not found in other rodents and may be unique to the mouse. The functional roles of PLPs remain to be deterrnined. 

The class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

Besides behavior and blood pressure, catecholamine neurons also have important roles in other brain functions. Regulation of neuroendocrine function is a well-known action of catecholamines for example, DA agonists reduce semm prolactin concentration, especially in conditions of hypersecretion. Ingestive behavior can be modulated by brain catecholamines, and some appetite-suppressing dmgs are beheved to act via catecholaminergic influences. Catecholamines also participate in regulation of body temperature. 

The growth hormone also binds to the prolactin receptor... 

The prolactin receptor, PER, which regulates milk production in mammals, belongs to the same receptor class as the growth hormone receptor. In addition to binding the hormone prolactin, PER also binds and is activated by growth hormone. The extracellular domain of PER forms a very stable 1 1 complex with growth hormone in solution this complex has been crystallized and its structure determined (Figure 13.21). We shall compare this structure with the 1 2 complex of the same hormone with GHR. 

Figure 13.22 Hormone-receptor interactions involving the domain-domain linker region in the receptor, (a) Interactions between the growth hormone (red) and the growth hormone receptor (blue) linker region. Glu 127 of the receptor forms a salt bridge to Arg 167 in the hormone, (b) The same interaction area in the growth hormone (red)-prolactin receptor (green) complex. The displacement of the linker region due to differences in the domain orientations have brought Asp 124 in the prolactin receptor into contact with Arg 167 of the hormone. (Adapted from W. Somers et al.. Nature 372 478-481, 1994.)...

There are five known classes of enzyme-linked receptors (1) receptor tyrosine kinases, which phosphorylate specific tyrosine residues on intracellular signaling proteins (2) tyrosine kinase-associated receptors, such as the prolactin and growth hormone receptors we have already discussed, which... 

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