Evidence for an Ultradian Secretion of Adrenocorticotropin, β-Endorphin and α-Melanocyte-Stimulating Hormone by the Ovine Anterior and Intermediate Pituitary

Abstract

These studies were undertaken to characterize the secretion of the pro-opiomelanocortin (POMC)-peptides adrenocorticotropin (ACTH), immunoreactive (ir)-β-endorphin (β-EP), and ir-α-melanocyte-stimulating hormone (ir-α-MSH) in the conscious sheep. When blood samples were taken at 10-min intervals, a distinct POMC-peptide and cortisol ultradian rhythm was observed, and 4 of the 7 possible POMC-peptide pulse patterns were defined. Three of these patterns included pulsatile ACTH secretion, and 70% were followed by a rise in plasma cortisol. The fourth pulse pattern consisted of concordant ir-β-EPand ir-α-MSH secretion and was not temporally correlated with cortisol secretion. When an intensified rate of venous sampling was used (2-min intervals over 1 h), the POMC-peptide and cortisol pulse frequencies were increased. Although the mean POMC-peptide and cortisol pulse amplitudes remained unaltered, the mean cortisol pulse amplitude was decreased. Five of the 7 possible POMC-peptide pulse patterns were noted, and 3 of these were identical to those observed during the 10-min sampling procedure. Chronic bromocriptine treatment decreased the plasma levels and pulse amplitudes of ir-β-EP and ir-α-MSH, increased the ir-β-EP pulse interval, and abolished concordant ir-β-EP and ir-α-MSHsecretion. Neither the plasma levels nor the ultradian rhythms of ACTH and cortisol were affected by the treatment. Chronic dexamethasone administration abolished the ACTH ultradian rhythm, reduced the plasma levels of ACTH, ir-β-EP, and ir-α-MSH, while plasma cortisol levels became undetectable. Although the ir-α-MSH interpulse interval was increased, the ir-β-EP and ir-α-MSH ultradian rhythms were not abolished. We conclude that: (1) an ultradian rhythm characterizes the secretion of ACTH, ir-β-EP, and ir-α-MSH from the ovine pituitary; (2) this rhythm is due to the pulsatile secretion of peptides from the adenohypophysis and intermediate lobe; (3) the adenohypophysis and intermediate lobes appear to secrete POMC-peptides in synchrony and asynchrony, and (4) intensified rates of venous sampling unmask the appearance of high-frequency POMC-peptide and cortisol pulses in vivo in the sheep.

Short-Term Secretion Patterns of Corticotropin-Releasing Hormone, Arginine Vasopressin and ACTH as Shown by Intensive Sampling of Pituitary Venous Blood from Horses

“…These fluctuations were not the product of assay noise, since no peaks were detected when one plasma pool was repeatedly assayed, while peaks were placed similarly when a series of samples front 1 horse were reassayed. Furthermore, peaks do not seem to be artifacts of variable dilution of pituitary with systemic blood, as deduced from mathematical modelling of some of the present data [24] and from our previous work in which secretion patterns of hormones from differ ent axes were found to be uncorrelated [ 14,25], Rather, it is most likely that the fluctuations represent the high fre quency ACTH micropulses observed by others in periph eral blood from rats [3,10], monkeys [2], goats [4], sheep [26] and humans [27], Micropulse frequency in horse PV blood was approximately 2-3 times that reported in peripheral blood from other species, but this was most likely due to our sampling close to pituitary meaning that small peaks of secretion were detected more easily. It could also be because our more intensive sampling regi men (20 or 30 s vs. 1 [2,10] or 2 [3,4,26,27] min) unmasked high frequency pulses, since when we simu lated slower sampling frequencies, significantly fewer CRH, AVP and ACTH peaks were observed.…”

Pulsatile ACTH and Cortisol in Goats: Effects of Insulin-Induced Hypoglycemia and Dexamethasone

“…Previous analyses of plasma ACTH and corti sol time series have demonstrated circadian changes in amplitude but not frequency of secretory pulses in rats [8], monkey [6], sheep [19], and humans [23,40], Ana lyses of time series of plasma ACTH concentrations have demonstrated alterations in both amplitude and fre quency in response to an experimental stress [7] and fol lowing CRH immunoneutralization [9,10], Engler et al [12][13][14] have done elegant work on pulsatile POMC pep tide secretion in sheep, a ruminant like goats. Most of their work has been done on 10-min measurements, which increases the likelihood of detecting an aliased rhythm rather than the actual signal [2], They have dem onstrated this themselves, by comparing 2-and 10-min sampling [12]. Two-minute sampling unmasked high-fre quency POMC-peptide and cortisol pulses undetectable by 10-min sampling.…”

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

“…Furthermore, episodic release of CRH has been shown in macaque (Mershon et al 1992), sheep (Caraty et al 1988, Engler et al 1989, and the rat (Ixart et al 1991(Ixart et al , 1994. The evidence of pulsatility of CRH led to the acceptance that the ultradian release of CORT was driven by a hypothalamic CRH pulse generator.…”