Pituitary Adenylate Cyclase-Activating Peptide-38 (Pacap)-38 Is Released Into Hypophysial Portal Blood in the Normal Male and Female Rat

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) was first isolated from ovine hypothalamus as two molecular forms, the basic 38 residue amidated peptide PACAP-38 and the N-terminal 27 amino acid sequence PACAP-27. A dense plexus of PACAP immunoreactive fibres is present in the internal and external layers of the median eminence and in other parts of the hypothalamus with PACAP cell bodies in the paraventricular and supraoptic nuclei. The present study shows, for the first time, that, as assessed by radioimmunoassay of extracted plasma, the amount of PACAP-38 in hypophysial portal is significantly greater than in peripheral blood, and that as assessed by reversed phase high performance liquid chromatography, PACAP 1-38 is the major form in portal blood. This evidence is crucial for the fact that PACAP-38 may be a hypothalamic-pituitary regulatory factor.

The Different Effects of I.c.v. Injection of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) on Prolactin Secretion in Adult Male and Lactating Rats

“…On the other hand, the PRL secretion and TH activity were not affected by the treatment of PACAP38 in lactating rats without suckling, suggesting that the sensitivity to PACAP is different depending on the physiological or endocrinological condition of the experimental animal model. It has been reported that the concentration of PACAP in hypophysial blood is higher in female than in male rats [3] and the density of the VIP binding site (type2-like PACAP receptor) is changed in the hypothalamus during lactation [18]. Considering these reference reports and our present data, the amount of endogenous PACAP and its receptor may change in response to sex steroid hormone or hormones present due to the suckling stimulus.…”

Identification of pituitary adenylate cyclase-activating polypeptide1-38-binding factor in human plasma, as ceruloplasmin

“…Potential functions of the binding protein could include blood transport of PACAP, altering of the PACAP clearance rate, inactivation of neuronal overflow to the blood of PACAP released at the synapses, increasing or decreasing biological activity of PACAP and, finally, targeting of PACAP. The high concentration of ceruloplasmin in human plasma (1.7 µM) compared with the reported picomolar concentrations of PACAP 1-38 in the circulation [37] (50-100 pM in hypophyseal portal plasma and 25 pM in peripheral plasma) implies a high binding capacity for PACAP despite the moderate apparent K d of 12.0 nM for the PACAP 1-38-ceruloplasmin complex. If ceruloplasmin serves as a transport protein for PACAP 1-38 in human blood, the moderate apparent K d enables PACAP 1-38 to dissociate from the protein and bind to a PACAP receptor.…”

Analysis of the In Vitro Secretory Activity of Human Pituitary Adenomas: Modification of Corticotropin Release from Adenoma Tissue Explant Cultures by Addition of a Human Plasma Ultrafiltrate Bioactive Fraction

“…It is possible that TBP (bioactive fraction of the human plasma ultrafiltrate) contains factor(s) involved in the stress reaction or paracrine regulation of the growth factor synthesis, thus indirectly affecting the hormone release, but these possibilities have to be further evaluated. Finally, it is not impossible that TBP, like some other bioactive peptides (29)(30)(31)(32)(33)(34)(35), is involved in regulation of adenylate cyclase activity and/or calcium metabolism, thereby acting as a regulator of the hormonal activity of the normal and tumourous pituitary tissue.…”