Presence of ACTH-Potentiating Factors in Rat Anterior Pituitary Glands

Abstract

High molecular weight ACTH fractions, obtained through gel filtration of boiled rat anterior pituitary extract, induced a marked increase in corticosterone production from isolated rat adrenal cells in the presence of low concentrations of ACTH-(1-24). This indicates the presence of heat-stable factors augmenting the steroidogenic action of ACTH in the rat anterior pituitary. We also noted that these factors potentiated the activity not only of ACTH-(1-24) but also of ACTH-(1–18). The ACTH-potentiating factors in rat anterior pituitary extract are possibly present in heterogeneous forms according to their molecular weights (8,000, 10,000 and 15,000), their mobility in ion-exchange chromatography and their content in RIA-ACTH activity. Of these three forms, the former comigrated with biological ACTH activity. The remaining two forms were free of it. Since the effect of potentiating factors on modified ACTH-(1–19), shown to be less susceptible to proteolytic degradation than ACTH-(l-24), was similar to the effect on ACTH-(1-24), it is suggested that potentiation was not due to an inhibition of ACTH proteolysis.

Presence of Adrenocorticotropin-Potentiating Activity in a Calcitonin Preparation Derived from Porcine Thyroid Glands

“…Large molecular weight frac tions also possessed minute amounts of RIA-ACTH alongside the ACTH-potentiating ac tivities found for various molecular weights. This shows similarities close to what was found for rat anterior pituitary glands [1]. The present study strongly suggests that an ACTH-potentiating factor might be con tained in the procine thyroid glands from which the calcitonin preparations were pre pared.…”

“…An ACTH-potentiating activity was also found for human pro-y-MSH fractions of the pre cursor by Ernad et al [3]. Taken together with our report [1], these indicate that an ACTH-LPH precursor might also be con tained in the thyroid gland. Furthermore, the heterogeneous molecular size distribution of this activity may also substantiate this possi bility.…”

“…Using an antiserum directed toward the 19-24 amino acid sequence of the ACTH molecule, radioim munoassay was carried out also as previously dc- scribed [1], Porcine ACTH-(l-39) was used as the standard. The assayable range of ACTH under this method was from 0.6 to 20 ng/ml.…”

“…We previously reported on the presence ofadrenocorticotropin (ACTH)-potentiating factors in rat anterior pituitary glands [1], This factor augmented the action of ACTH on steroidogenesis in isolated rat adrenocor tical cells in vitro. Known pituitary hor mones were investigated for this activity.…”

The Role of Modern Bioassays in Clinical Endocrinology

“…The situation can become even more complex. If molecules derived from the N-terminal sequence of pro-opiomelanocortin are responsible (together with ACTH) for the maintenance of adrenal growth and division (Lowry, 1984) then an assay based upon cortisol secretion from adrenal cells, itself possibly the result of a complex interaction of many molecules with ACTH (Pederson & Brownie, 1980;Pederson et al, 1980;Al-Dujaili et al, 1981;Iida et al, 1981Iida et al, , 1982Iida et al, , 1984Parker et al, 1983;Morita et al, 1984) will not necessarily be relevant to a question about adrenal growth. In the context of the pituitary adrenal axis it may be that until our understanding of this complex system improves, different bioassays are required which supply information about the total cortisol-releasing and adrenal growth-promoting activities in blood, as well as immunoassays of ACTH itself.…”