Corticotrophs

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... 

Samson WK, Taylor MM. Hypocretin/orexin suppresses corticotroph responsiveness in vitro. Am J Physiol Reg Int Comp Physiol 2001 281 R1140-1145. 

Phenobarbitone, benzodiazepines Valproate, benzodiazepines, adreno-corticotrophic hormone Ethosuximide, valproate, benzodiazepines, acetazolamide... 

It can also be seen that preincubation with the potent glucocorticoid dexaraethasone under conditions which lead to an almost complete inhibition of ACTH secretion in corticotrophs of the anterior pituitary gland (85), has no inhibitory effect on either spontaneous or CRF-induced a-MSH secretion. 

Corticotropin-releasing hormone (CRF) AC stimulation Gs corticotroph, hypothalamus... 

Grino M, Guillaume V, Boudouresque F, Margioris AN, Grisoli F, Jaquet P, Oliver C, Conte-Devolx B (1988) Characterization of corticotropin-releasing hormone receptors on human pituitary corticotroph adenomas and their correlation with endogenous glucocorticoids. J Clin Endocrinol Metab 67(2) 279-83... 

Two neuropeptides, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) are released from parvoceUular neurons in the hypothalamic PVN to initiate a stress response. The terminal endings of these neurons, located in the median eminence of the hypothalamus, release CRH and AVP into the hypothalamic-hypophysial portal vessel system, where they travel to the anterior pituitary. The two neuropeptides act syn-ergistically on pituitary corticotrophs to activate the synthesis of pro-opiomelanocortin (POMC). This peptide, discussed in detail below, is processed to produce several peptides including adrenocorticotrophic hormone (ACTH), or corticotropin. ACTH released from corticotrophs travels via the bloodstream to act on cells in the zona fasciculata layer of the adrenal cortex, stimulating the synthesis and release of the glucocorticoids, cortisol (in humans) or corticosterone (in rodents). 

Lopez JA, Kleinschmidt-Demasters Bk B, Sze Cl, Woodmansee WW, LiUehei Silent corticotroph adenomas Further clinical and pathological observations. Hum Pathol 2004 35 1137-47. 

The mechanism by which ACTH acts on learning and memory is not clear. The hormonal action does not, however, appear to depend on adrenocortical activity. Many studies have demonstrated that melanonyte stimulating hormone, which shares a behaviorally active peptide sequence with ACTH, as well as several N-terminal ACTH analogs (e.g., ACTH q [Met-Glu-His-Phe-Arg-Try-Gly]) which have no corticotrophic activity, have effects on learning, memory, and maintenance lfjjrn performance which are quite comparable to those of ACTH itself. Recent studies have examined the... 

Adrenocorticotropic Hormone (ACTH) (Corticotropin) Anterior Pituitary (Corticotroph) 39 aa 2p25 Stimulates steroidogenesis in all three zones of the adrenal cortex, thereby increasing secretion of cortisol, DHEAS, and aldosterone. Stimulated by CRH and inhibited by cortisol. 

After translation POMC is processed by proteases contained in tissue. In the adenohypophyseal corticotrophs there is no further processing of ACTH and y3-endorphin, whereas in the intermediate lobe of other species, ACTH can be processed to form a-MSH, and y-LPH can be processed to form 6-MSH. The human hypothalamus... 

Cortisol is produced by the adrenal gland under the precise control of the hypothalamus and pituitary. The hypothalamus secretes corticotropin-releasing hormone (CRH) in response to stress. CRH acts on plasma membrane receptors in corticotrophic cells in the anterior pituitary to stimulate their release of... 

Silent corticotroph cell adenoma (subtypel) 2.0 ACTH p-end (P-end>ACTH)... 

Besedovsky first showed in 1986 (B35) that rIL-ip increased ACTH and cortisol levels in mice. Corticotrophic cells from pituitaries incubated with IL-1 confirmed that it is a potent secretagogue for ACTH. In vivo increases in ACTH and corticosterone were blocked by antibodies to CRF, implying a hypothalamic site of action. lL-1 is also able to induce corticosteroine release directly from adrenal gland cells (S4, S5) but rIL-6 is even more potent in this respect and it synergizes with low concentrations of ACTH (S5). 

The oxidative reactions that lead to the synthesis and secretion of glucocorticoids such as cortisol are stimulated by adrenal corticotrophic hormone (ACTH). The role of cortisol as a stress-released hormone is discussed in Chapter 43. 

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