Adrenocorticotropic hormone peptides

Pregnenolone is transported from the mitochondria to the ER, where a hydroxyl oxidation and migration of the double bond yield progesterone. Pregnenolone synthesis in the adrenal cortex is activated by adrenocorticotropic hormone (ACTH), a peptide of 39 amino acid residues secreted by the anterior pituitary gland. 

Proopiomelanocortin (POMC) is the precursor peptide of hormones and neuropeptides expressed in the pituitary and the hypothalamus (adrenocorticotropic hormone (ACTH), lipotropin, a-melanocyte-stimulating hormone (aMSH), yMSH, 3-endorphin, and others). The main clinical consequences of POMC deficiency are adrenal insufficiency (due to absence of ACTH), red hair pigmentation (due to absence of MSH) and severe early-onset obesity (due to the lack of aMSH). 

FIGURE 1 8-5 Tissue-specific processing of the pro-opiomelanocortin (POMC) precursor yields a wide array of bioactive peptide products. Processing of the POMC precursor varies in various tissues. In anterior pituitary, adrenocorticotropic hormone (ACTH (1-39)) and P-1 ipo tropin (P-LPH) are the primary products of post-translational processing. Arcuate neurons produce the potent opiate P-endorphin (P-endo (1-31)) as well as ACTIK1 -13) NIT,. Intermediate pituitary produces a-melanocyte-stimulating hormone (aMSH), acetylated P endof 1 31) and P-endo(l-27). NTS, nucleus tractus solitarius. 

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. 

As would be expected of active protein secreting cells, glandular epithelial tissue, the cytokine secreting cells of the immune system and the blood vessel endothelium, have an extensive internal structure consisting of rough endoplasmic reticulum and numerous mitochondria. Peptide hormones, growth factors and cytokines like all proteins are synthesized by DNA transcription and mRNA translation. The primary transcript of the mRNA may code for an inactive prohormone which requires careful proteolysis to produce the active hormone, as for example in the case of insulin. Adrenocorticotropic hormone (ACTH) is particularly interesting in this respect because... 

The relationship between the structure of a series of peptides derived from the adrenocorticotropic hormone ACTH, and the behavioural activity in an active avoidance behaviour test, has been studied over the past 10-20 years. The results obtained were quite different from those in which endocrine activity relationships were studied. From the outcome of a quantitative study on the structure--behavioural activity of the ACTH-related peptides, suggestions about the spatial interactions at the receptor site were made. This receptor-bound conformation differed from those suggested by solution experiments or found in crystal structures. 

Hydroxytryptamine (5-HT), dopamine, and norepinephrine play important roles as central neurotrans-mitters in the process of erection. Still other substances or hormones, such as endorphins, oxytocin, vasopressin, adrenocorticotropic hormone (ACTH) and related peptides, and prolactin, appear to participate in the complex and coordinated process of penile erection. Central nonadrenergic neurons also may influence male sexual behavior. 

Bhatt NP, Patel K, Borchardt RT. Chemical pathways of peptide degradation. I. Deamidation of adrenocorticotropic hormone. Pharm Res 1990 7(6) 593-599. 

Anterior Lobe. The anterior pituitary, or adenohypophysis, secretes six important peptide hormones. The anterior pituitary releases growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and prolactin (Pr). The physiologic effects of these hormones are listed in Table 28-1. 

There are dozens of presynaptic receptors for endogenous peptides. This review will focus on receptors for four peptides or peptide families the opioid peptides, neuropeptide Y and related peptides, adrenocorticotropic hormone (corticotropin, ACTH), and the orexins. This choice is representative, since part of the receptors inhibit and part of them facilitate transmitter release moreover, the receptors under consideration are coupled to the major G proteins, namely Gl/(), Gs and Gq (Table 1). 

Naunyn-Schmiedeberg s Arch Pharmacol 338 368-72 Szabo B, Hedler L, Starke K (1989) Facilitation of the release of noradrenaline an extra-adrenal effect of adrenocorticotropic hormone. Resuscitation 18 229-42 Tatemoto K (2004) Neuropeptide Y history and overview. In Michel MC (ed) Neuropeptide Y and related peptides, Handbook of Experimental Pharmacology, vol 162. Springer, Berlin, pp 1-21 Tatemoto K, Carlquist M, Mutt V (1982) Neuropeptide Y - a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 296 659-60... 

Several of the small physiologically active peptides now are known to be derived from a single protein precursor synthesized by the pituitary gland (43). As shown in Figure 9, ACTH (adrenocorticotropic hormone), /3-LPH ( -lipotropic hormone), /3-MSH ( -melanocyte-stimulating hormone), /3-endorphin, and enkephalin result from the specific proteolytic cleavage of a precursor protein of approximately 8,000 daltons. 

Adrenocorticotropic hormone (ACTH) Polypeptide with 39 amino acids Corticotropin-releasing hormone (CRH) peptide with 41 amino acids Unknown Causes release of steroid hormones from adrenal cortex... 

ACTH (adrenocorticotropic hormone, corticotropin) is a 39-amino-acid peptide synthesized and secreted by the corticotrope cells of the anterior lobe of the pituitary gland. ACTH acts on several target tissues, including the adrenal cortex, adipose tissue and brain. It is synthesized as part of proopiomelanocortin (POMC) as amino acids 132-170 of this molecule, which is proteolytically cleaved to produce ACTH [1],... 

Van der Vies (1957) Experience with an assay of adrenocorticotropic hormone based on the steroid output of rat adrenals in vitro. Acta Physiol Pharmacol Neerl 5 361-384 Vogel (1969) Tierexperimentelle Untersuchungen iiber syn-thetische Peptide mit Corticotropinaktivitat. A Vergleich mit dem III. Internationalen Standard fur Corticotropin. Arzneim Forsch/Drug Res 19 20-24... 

Mezey E, Kiss JZ, Mueller GP, Eskay R, O Donohue TL, Palkovits M (1985) Distribution of the pro-opiomelanocortin derived peptides, adrenocorticotrope hormone, a-melanocyte-stimulating hormone and P-endorphin (ACTH, a-MSH, P-END) in the rat hypothalamus. Brain Res 525 341-347. 

Hormones Gastrointestinal (e.g. vasoactive intestinal peptide VIP), pituitary (e.g. adrenocorticotropic hormone ACTH), pancreatic (e.g. insulin), parathyroid (e.g. parathyroid hormone), reproductive (e.g. hCG), thyroid (e.g. thyroxine)... 

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