Lactation as a model for naturally reversible hypercorticalism plasticity in the mechanisms governing hypothalamo-pituitary- adrenocortical activity in rats.

Abstract

Steady state levels of hypothalamic expression of the genes encoding corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), arginine vasopressin (AVP), and oxytocin (OT) were studied in rats to investigate the mechanisms underlying the transitions between hypercorticalism during lactation and normocorticalism upon weaning. During lactation, CRH mRNA levels and blood titers of adrenocorticotropin (ACTH) were found to be significantly reduced, although POMC mRNA levels in the anterior pituitary were not significantly different from those found in cycling virgin (control) rats; during all phases of lactation, an inverse relationship was observed between the blood levels of ACTH and corticosterone (CORT). Plasma prolactin (PRL) concentrations were elevated 30-fold during lactation. Whereas steady state levels of OT mRNA were markedly increased throughout lactation, those of AVP mRNA were only transiently (initially) elevated, and the blood levels of these hormones were not significantly altered in lactating as compared with cycling virgin and postlactating rats. CRH and POMC gene expression and blood levels of ACTH, CORT, and PRL were normalized within 1-3 d of removal of suckling pups. The temporal relationships between the biosynthetic profiles of the various peptide hormones and the patterns of ACTH and CORT secretion during the two physiological states suggest that lactation-associated hypercorticalism does not merely result from increased ACTH secretion; although still not well substantiated at this time, the evidence points to contributory roles of PRL, OT, and AVP in the hypercorticalismic state found during lactation. (J. Clin. Invest. 1995.96:1208-1215

Blunted HPA axis response in lactating, vasopressin-deficient Brattleboro rats

“…As a consequence, the hypothalamic feedback on CRH secretion is removed, which leads to an enhanced activation of brain CRH peptide synthesis (O'Keane et al 2011). Our finding of an enhanced expression of Crh mRNA in the PVN is similar to the findings of a study carried out in 3-day-old lactating rats of the Sprague Dawley strain (da Costa et al 2001) and are in accordance with higher Crh mRNA levels found in the PVN of chronically stressed animals (Pournajafi-Nazarloo et al conditions (Fischer et al 1995, Brunton et al 2008. As the CRH levels were found to be low during pregnancy (Neumann et al 1998) and HPA axis reactivity was restored within 2 days of pup removal (Walker et al 1992, Toufexis et al 1999, it can concluded that the stage of the lactation period obviously influences the outcome of this type of analysis.…”

“…It is worth noting that although ACTH is derived from POMC, we failed to detect significant differences in resting plasma ACTH levels. Obviously, the increased synthesis of the precursor mRNA is not necessarily paralleled by a similarly increased release of ACTH, as has been suggested earlier (Fischer et al 1995). Further studies have to determine whether an enhanced synthesis of Pomc mRNA may provide an alternative marker for a chronic stress state (Makara et al 2012).…”

“…2). Fischer et al (1995) reported that Pomc mRNA levels in the adenohypophysis of Wistar rats are elevated only during the first day of lactation and then return to levels observed in virgin rats. At present, it is difficult to explain the difference between the two observations.…”

“…2D; Fischer et al 1995). The absence of this increase in Avp-deficient mothers suggests a relevant role for hypothalamic AVP in the maintenance of hypercorticism during lactation.…”

Attenuated neuroendocrine responses to emotional and physical stressors in pregnant rats involve adenohypophysial changes

“…During lactation, the activity and regulation of the HPA axis are altered in ways that are dependent on the presence or suckling of the young (Walker, Lightman, Steele & Dallman, 1992;Windle et al 1997). Thus, an increase in glucocorticoid secretion and a flattening of the diurnal rhythm in glucocorticoid secretion have been described (Stern, Goldman & Levine, 1973;Walker et al 1992;Fischer, Patchev, Hellbach, Hassan & Almeida, 1995). In addition, secretion of ACTH from the anterior pituitary and, consequently, of cortisol (humans) and corticosterone (rats) from the adrenal glands is reduced during physical (Altemus, Deuster, Galliven, Carter & Gold, 1995;Walker, Trottier, Rochford & Lavall ee, 1995), ether (Lightman & Young, 1989;Walker et al 1992) and noise stress (Windle et al 1997), and in response to cardiovascular stimuli (Keller-Wood, 1996).…”