Comparison of Adrenocorticotropin Control in Brattleboro, Long-Evans, and Wistar Rats

Abstract

The purpose of this study was to compare the control of adrenocorticotropin (ACTH) and corticosterone secretion in homozygous Brattleboro rats with their syngeneic controls, Long-Evans rats, and with rats of the Wistar strain. Plasma concentrations of ACTH and corticosterone were measured by radioimmunoassay in trunk blood, and corticotropin-releasing factor 41 (CRF-41), arginine vasopressin (AVP), and oxytocin were assayed in hypophysial portal vessel blood. Portal plasma was extracted with methanol for CRF-41 determination, and four different antisera and several different high-performance liquid chromatography (HPLC) systems were used to investigate AVP release. The peripheral plasma concentrations of ACTH and corticosterone were significantly higher in Long-Evans and homozygous Brattleboro than in Wistar rats. This difference was due, at least in part, to an approximately twofold greater release of CRF-41 into hypophysial portal blood of the Long-Evans and Brattleboro compared with Wistar rats. There was no significant difference between the strains in the output of oxytocin into portal blood. While no AVP could be detected in the neural lobe of homozygous Brattleboro rats, a small amount of AVP-like immunoreactivity was detected in unextracted hypophysial portal blood from homozygous Brattleboro rats. However, this AVP-like immunoreactivity was clearly distinct from authentic AVP in several HPLC systems, had no antidiuretic activity, and on gel filtration had a relative molecular mass greater than 5 kD. In contrast, the AVP-like immunoreactivity in hypophysial portal blood from Long-Evans rats co-eluted with authentic AVP in all HPLC systems tested. These findings show that in the homozygous Brattleboro rat authentic AVP is not released into hypophysial portal blood and that, therefore, the normal plasma concentrations of ACTH in this mutant are maintained by CRF-41 and possibly other hypothalamic and/or pituitary factors which facilitate ACTH release.

Impaired Histamine- and Stress-Induced Secretion of ACTH and β-Endorphin in Vasopressin- Deficient Brattleboro Rats

“…Basal A C T H and p -E N D levels were the same in DI and L E rats. For A C T H this is in agreement with some studies [24,26] while other studies have shown lower basal A C T H levels in D I rats when compared to LE rats [27][28][29].…”

“…1038 Kjaer/ Knigge/Bach/Warberg Histamine, Stress and Brattleboro Rats Tlie plasma levels o f A C T H and p -E N D in LE rats were consistently 30-50% higher after these stimuli than the plasma levels previously observed in Wistar rats under going the same treatment [17]. This might be due to the higher C R H levels found in portal blood o f LE rats as compared to Wistar rats [24]. The different A C T H and p -E N D response in LE and Wistar rats stresses, in agree ment with previous reports [25], the necessity o f using the isogenic L E strain as control when studying the A C T H and [T E N D response to H A or stress stimulation in D I rats.…”

60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: Harris' neuroendocrine revolution: of portal vessels and self-priming

“…A similar 20-to 50-fold increase in pituitary responsiveness to GnRH also occurs in the human between the early follicular and mid-cycle phases (Yen et al 1972). The increase in pituitary responsiveness initiated by oestrogen is further augmented by progesterone secreted during the early part of the LH surge and, more importantly, by the self-priming effect of GnRH, the unique capacity of the decapeptide to increase pituitary responsiveness to itself Aiyer et al 1974b, Fink 1988, 1995b. The role of the GnRH self-priming effect appears to be crucial for ensuring the coincidence of the GnRH surge with the increase in pituitary responsiveness to GnRH so that both events reach a peak simultaneously and, as a consequence, produce a massive ovulatory surge of LH.…”

“…The history of neuroendocrinology has been the subject of several reviews (Harris 1955, Guillemin 1967, 1978, 2011, Harris 1972, 1986, 1988, Charlton 2008. Friedgood (1936) and Hinsey (1937) were arguably the first to postulate formally that the anterior pituitary gland was controlled by substances liberated into the hypophysial portal vessels from nerve terminals in the median eminence.…”

“…Thus, for example, pulsatile growth hormone (GH) secretion is stimulated by GH-releasing hormone, potentiated by the GH secretagogue, ghrelin, and inhibited by somatostatin (Veldhuis et al 2012). Arginine vasopressin potentiates CRF-41 action in the release of corticotrophin (Fink et al 1988, Tannahill et al 1988, Antoni 1993, Aguilera 2011. Pulsatile GnRH, and therefore gonadotrophin secretion, in mammals might be generated by a subpopulation of kisspeptin neurons within the arcuate nucleus that co-express neurokinin B (the gene product of the tachykinin family member TAC3) and dynorphin.…”