Lack of Correlation Between Immunoreactive Corticotropin‐Releasing Factor Concentration Profiles in Hypophysial‐Portal and Peripheral Plasma

Abstract

Corticotropin-releasing factor (CRF-41) is the primary mediator of adrenocorticotropin secretion from the adenohypophysis. This 41-amino-acid peptide is synthesized in perikarya of the paraventricular nuclei, transported to nerve terminals in the external zone of the median eminence and released into the hypophysial-portal circulation. It is also synthesized in multiple extrahypothalamic and peripheral sites. In addition, immunoreactive (ir) CRF-41 is present in the systemic circulation, raising the possibility that systemic measurements might provide a useful index of hypothalamic irCRF-41 secretion. This hypothesis was tested in several rat models. Neither bilateral destruction of hypothalamic irCRF-41 producing perikarya, nor infundibular stalk transection altered peripheral plasma irCRF-41 concentration. Furthermore, central administration of norepinephrine, an agent previously shown to evoke irCRF-41 secretion into the portal circulation, was without effect on peripheral irCRF-41 concentration. Finally, while increased irCRF-41 levels in both the hypophysial-portal and the peripheral circulation were associated with nitroprusside-induced hypotension, bilateral paraventricular nuclei lesions blocked irCRF-41 secretion into the hypophysial-portal circulation without blunting the rise observed in the peripheral circulation. The source of peripheral irCRF-41 remains undetermined; however, the adrenals may be excluded as bilateral adrenalectomy failed to alter circulating irCRF-41 levels. Therefore, our observations do not support the concept that peripheral irCRF-41 levels provide a useful index of hypothalamic secretion of this peptide into the hypophysial-portal circulation under the conditions tested.

The central distribution of a corticotropin-releasing factor (CRF)-binding protein predicts multiple sites and modes of interaction with CRF.

“…Data from immunoand hybridization histochemical preparations were consistent in indicating a virtual absence of CRF-BP expression in the (medial parvocellular) region of the paraventricular nucleus of the hypothalamus, which is acknowledged as the predominant source of CRF in portal blood (19). Of the other clusters of magno-and parvocellular neurosecretory neurons that might be capable of delivering secretory products to the pituitary, only the arcuate and anterior periventricular nuclei contained small complements of CRF-BP-expressing neurons.…”

“…By contrast, the septal, preoptic, and hypothalamic regions all contained relatively few positively hybridized or immunostained cells, except for focally dense accumulations in the bed nucleus of the stria terminalis and the dorsomedial and ventral premammillary nuclei. It is noteworthy that expression in neurosecretory cell groups, particularly the paraventricular nucleus, the principal source of CRF in portal plasma (19), was generally limited to a few scattered cells.…”

Hair cycle-dependent expression of corticotropin-releasing factor (CRF) and CRF receptors in murine skin

“…Ovine (o) CRF, human (h) CRF, hCRF , [Gly 42 ]-hCRF [31][32][33][34][35][36][37][38][39][40][41][42] , [Gly 11 ]-hCRF [1][2][3][4][5][6][7][8][9][10][11] , [Gly 26 ]-hCRF [16][17][18][19][20][21][22][23][24][25][26] , [Gly 31 ]-hCRF [21][22][23][24][25][26][27][28][29][30][31] , and [Gly 36 ]-hCRF [26][27][28][29][30][31][32]…”

“…The rabbit antiserum RII used was directed toward the carboxyl-terminal sequence of hCRF and cross-reacted with hCRF(Ox), hCRF (100%), [Gly 42 ]-hCRF [31][32][33][34][35][36][37][38][39][40][41][42] (0.05%), oCRF (0.06%), carp urotensin (0.005%), and frog sauvagine (1.8%). None of the following showed any cross-reactivity (less than 0.002%): partial sequences [Gly 11 ]-hCRF 1-11 , [Gly 26 ]-hCRF [16][17][18][19][20][21][22][23][24][25][26] , [Gly 31 ]-hCRF [21][22][23][24][25][26][27][28][29][30][31] , [Gly 36 ]-hCRF [26][27][28][29][30][31][32][33][34][35][36] , the related peptide urocortin, the peptide hormones somatostatin, thyrotropin-releasing hormone, growth hormone-releasing factor, luteinizing hormone-releasing hormone, substance P, Leu-enkephalin, Met-enkephalin, human b-endorphin, b-casomorphin, angiotensin I, human growth hormone, thyroidstimulating hormone, follicle-stimulating h...…”

Cushing's syndrome associated with ectopic production of corticotrophin‐releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma

“…Hormone levels were measured by standard radioimmunoassay technique. Plasma was extracted for CRH measurement as described by Plotsky et al (1990). CRH radioimmunoassay was performed as previously described (Vale et al, 1983).…”