Effects of Amylin and Salmon Calcitonin on β-Endorphin-Induced Growth Hormone and Prolactin Secretion in the Rat

Abstract

In this study we examined the possible interplay of amylin (AMY) and salmon calcitonin (sCT) in the central control of growth hormone (GH) and prolactin (PRL) secretion in male rats. For this purpose we first compared effects of central intracerebroventricular (i.c.v.) admininstration of various doses of AMY (2.5–2,500 ng/rat) and sCT (2.2–220 ng/rat) on β-endorphin (β-END, 0.5 µg/rat)-induced GH and PRL secretion. AMY and sCT dose-dependently inhibited β-END-induced GH secretion, whereas only sCT was able to inhibit β-END-induced PRL secretion. To examine whether the GH inhibitory effect of AMY was due to the possible cross-reactivity of AMY and sCT on the same receptors in the CNS, we pretreated some rats with the AMY antagonist (AMY_8–37, 2.5 µg/rat, i.c.v.). AMY_8–37 significantly enhanced the GH-stimulatory action of β-END. AMY_8–37, administered prior to AMY and sCT, significantly removed the inhibitory effect of both AMY and sCT on β-END-induced GH release, suggesting that both peptides mediate their response on GH through a common receptor. In vitro competition binding studies on rat hypothalamic membranes have shown that both AMY and sCT compete with [¹²⁵I]rAMY binding with half inhibition (IC₅₀) values of 3.6 × 10^–11 and 1.6 × 10^–10 M, respectively. Binding of [¹²⁵I]sCT was inhibited by sCT with an IC₅₀ of 1.09 × 10^–10M and to a lesser extent by AMY with an IC₅₀ of 1.3 × 10^–6 M. Thus it is possible that the two peptides recognize a common hypothalamic receptor but with different affinities (sCT > AMY). Overall these data indicate that AMY behaves as a mimic of sCT in the central control of GH secretion. The failure of AMY, at variance with sCT, to modify the PRL-releasing activity of β-END indicates that different receptor subtypes for sCT are involved in the endocrine effects of sCT and only those mediating the modulatory action of GH respond to AMY.

In vitro autoradiographic localization of calcitonin and amylin binding sites in monkey brain

“…Amylin and CTs induce a number of potent effects when administered into the CNS including hyperthermia, adipsia, decreased appetite, modulation of extrapyramidal motor function and decreased growth hormone and gastric acid secretion (Sexton, 1991;Chance et al, 1991Chance et al, , 1991Balasubramaniam et al, 1991;Pagani et al, 1998;Sexton and Perry, 1996;Barth et al, 2003;Baldo and Kelley, 2001;Lutz et al, 1998aLutz et al, ,b, 2001Riediger et al, 1999). These actions are consistent with the high density of amylin and CT binding sites within the hypothalamus and accumbens nucleus and indeed can be mimicked, Fig.…”

“…In inducing anorexia and adipsia the mammalian CTs are relatively weak, and we have speculated that the actions of CTs, in generating these effects, may occur via amylin receptor phenotypes (Sexton and Perry, 1996). Recent data suggest that the central action of amylin and sCT in modulating ␤-endorphin-induced growth hormone secretion may occur via a common receptor with this action being attenuated by the weak amylin receptor antagonist amylin (8-37) (Pagani et al, 1998). Indeed, central amylin (8-37) alone enhanced ␤-endorphin stimulated growth hormone release, suggesting modulation of this pathway by an endogenous central amylin-like peptide (Pagani et al, 1998).…”

“…Recent data suggest that the central action of amylin and sCT in modulating ␤-endorphin-induced growth hormone secretion may occur via a common receptor with this action being attenuated by the weak amylin receptor antagonist amylin (8-37) (Pagani et al, 1998). Indeed, central amylin (8-37) alone enhanced ␤-endorphin stimulated growth hormone release, suggesting modulation of this pathway by an endogenous central amylin-like peptide (Pagani et al, 1998). In contrast, only sCT-inhibited ␤-endorphin mediated prolactin release indicating that this was likely due to an independent CT receptor.…”

“…Amylin has been proposed as an endocrine partner to insulin in metabolic regulation . In addition, centrally administered amylin induces potent effects including anorexia, adipsia, decreased gastric acid and growth hormone secretion and reduced gastrointestinal motility (Chance et al, , 1992Balasubramaniam et al, 1991;Pagani et al, 1998;Sexton and Perry, 1996;Barth et al, 2003;Baldo and Kelley, 2001;Lutz et al, 1998aLutz et al, ,b, 2001Riediger et al, 1999), suggesting that amylin or its receptors may also be involved in the regulation of body energy balance. Indeed, the site of action of the anorectic effect of peripherally administered amylin has recently been localized to the area postrema/solitary nucleus region of the brain (Lutz et al, 1998a,b;Rowland and Richmond, 1999), an area exhibiting a deficient blood-brain barrier.…”

Oral salmon calcitonin – pharmacology in osteoporosis

“…Furthermore, data from patients with crush fractures showed that nasal salmon CT (200 IU) provided greater pain relief than intramuscular injection, as early as 7 days after the first drug administration. The analgesic effect is associated with an elevation of the circulating levels of b endorphin, which seems to be higher with the nasal form [80,98,[103][104][105] than with intramuscular administration.…”