Taeko Hirose

Adrenal cortical secretion in response to pilocarpine in dogs with hypothalamic lesions.

Adrenal venous blood samples were collected from conscious and anesthetized dogs before and after an injection of pilocarpine and were analyzed for 17-hydroxycorticosteriods (17-OHCS). In conscious dogs the adrenal 17-OHCS secretion rate increased from a pre-injection secretion rate of 0.11 plus or minus 0.014 to 1.58 plus or minus 0.069 (mean plus or minus SE) mug/kg/min following an intravenous injection of pilocarpine (0.3 mg/kg); there was a return to the baseline level by 120 min. In anesthetized dogs a marked increase in adrenal 17-OHCS secretion was also observed, which was completely abolished by hypophysectomy A noticeable impairment of the adrenocortical response to pilocarpine was found to be produced by radio-frequency-current lesions of the anterior median eminence. A partial depression of the response was also observed in dogs with the anterior ventromedial hypothalamic lesions. Lesions destroying other hypothalamic areas were found to be without significant effect upon the adrenal cortical secretory response to pilocarpine.

Effect of platelet-activating factor on cortisol and corticosterone secretion by perfused dog adrenal

Administration of platelet-activating factor (PAF) to perfused adrenal increased cortisol and corticosterone secretion. With hexadecyl PAF (C16PAF; 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine), the increase was significant at 1 nM and maximal at 10 nM. The responses to 10 nM octadecyl PAF (C18PAF; 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) were one fourth of those to 10 nM C16PAF. The addition of C16PAF to dispersed adrenal cells significantly increased cortisol and corticosterone production at 0.1 nM and 10 nM, respectively. C16PAF was about 1000 times more potent than histamine on a molar basis in respect to cortisol response in both perfused adrenal and dispersed adrenal cells. The results suggest that PAF induces cortisol release from dog adrenal.

Adrenal Cortical Secretory Responses to Histamine and Cyanide in Dogs with Hypothalamic Lesions

Experiments were performed on dogs with hypothalamic lesions as well as on intact and hypophysectomized dogs. Adrenal venous blood samples were collected and analyzed for 17-hydroxycorticosteroids (17-OHCS). In intact dogs, a marked increase in adrenal 17-OHCS secretion was observed after an i.v. injection of histamine and following an i.v. infusion of cyanide. Adrenal 17-OHCS secretion in response to histamine was markedly reduced but not completely abolished by hypophysectomy and was partially impaired by anterior median eminence lesions and by posterior median eminence lesions, but was not significantly impaired by supramammillary lesions. Adrenal 17-OHCS secretion in response to cyanide was completely abolished by hypophysectomy, markedly reduced by posterior median eminence lesions and partially impaired by anterior median eminence lesions and by supramammillary lesions. Thus, a partial dissociation of the adrenocortical secretory responses to histamine and cyanide was observed in dogs with hypothalamic lesions, suggesting that the mechanism and the pathway to the anterior pituitary involved in the adrenocortical secretory response to histamine and cyanide are somewhat different.

Dissociation of Adrenocortical Secretory Responses to Cyanide and Pilocarpine in Dogs with Hypothalamic Lesions

In dogs with hypothalamic lesions as well as in intact and hypophysectomized dogs, adrenal venous blood samples were collected and analyzed for 17-hydroxycorticosteroids (17-OHCS). In intact dogs a marked increase in adrneal 17-OHCS secretion was observed following the i.v. infusion of cyanide as well as after the i.v. injection of pilocarpine; this was completely abolished by hypophysectomy. The adrenocortical response to pilocarpine was markedly impaired and that to cyanide partially suppressed after lesioning of the anterior median eminence. However, after lesioning of the posterior median eminence, the adrenocortical secretory response to pilocarpine was almost the same as in intact dogs, whereas the response to cyanide was markedly impaired. Thus, a dissociation of adrenocortical secretory responses to cyanide and pilocarpine was demonstrated in dogs with hypothalamic lesions.

Effect of PAF receptor antagonists on adrenocortical secretion induced by ACTH in normal and athymic nude mice

The effect of SM12502 and CV6209, platelet-activating factor (PAF) receptor antagonists on corticosterone (B) secretion induced by ACTH was examined in the perfused adrenals of CD1 ICR (normal) and CD1 ICR nu/nu (athymic) mice. Bilateral adrenals were perfused in situ with an artificial medium equilibrated by 95% O2 + 5% CO2. Continuous infusion of 10 microM SM12502 or CV6209 inhibited the B response to 100 pg/ml ACTH markedly in normal mice but insignificantly in athymic mice. Infusion of PAF did not significantly affect B secretion in either normal or athymic mice. Administration of 0.1 microM of N-methylcarbamyl PAF, a nonmetabolizable PAF agonist, significantly increased B secretion in normal mice, but not in athymic mice. Infusion of SM12502 significantly depressed the B response to 10 microM forskolin or 1 mM dibutyryl cyclicAMP (cAMP) in normal mice, but not in athymic mice. The results indicate that endogenous PAF and its receptor may play a role in the ACTH-initiated signaling pathway at the phase after responsiveness to cAMP and its receptor may have little function in athymic mice.

Adrenal 17-hydroxycorticosteroid secretion in response to alloxan in unanaesthetized dogs.

as evident by their less n u m b e r and degranula t ion of cytop lasm. F r o m J a n u a r y onwards the cyanophils of the p i tu i t a ry increase in n u m b e r and become granulated gradually. Coinciding wi th the onset of act ivi ty of cyanophils, the gonads emba rk upon their p r epa ra to ry phase and show new crop of germ ceils. These ge rm ceils s t a r t developing and b y the m o n t h of June , t hey reach the advanced stage of matura t ion . Thus by the end of Augus t intense act iv i ty occurs bo th in the p i tu i t a ry gland and the gonads and they are ready for the nex t breeding season. The close relat ion between the seasonal histological changes of the p i tu i ta ry and gonads gets fur ther suppor t f rom the parallel range of var ia t ion of the stat ist ical da ta of the gonosomat ic index and ova diameter on the one hand and average cyanophilic cell area on the other. My grateful t hanks are due to Prof. H. SWARUP under whose guidance the work is being carried out. The financial assistance rendered by Council of Scientific and Indus t r ia l Research, New Delhi, is gratefully acknowledged.

Cross-regulation of cortisol secretion by adrenocorticotropin and platelet-activating factor in perfused guinea pig adrenals.

We examined the cross-regulation of signaling between ACTH-and platelet-activating factor (PAF)-mediated steroidogenesis in the perfused guinea pig adrenal gland. Our method of in situ perfusion using an artificial medium can evaluate whether cortisol secretion in response to ACTH and PAF is interactive. Treating adrenal glands with 100 pg/ml ACTH diminished the subsequent cortisol response to 10 nM PAF. By contrast, PAF resulted in subsequent potentiation of ACTH-induced cortisol secretion. A mixture of 50 microM L-alpha-1-oleoyl-2-acetyl-sn-glycerol (OAG), an activator of protein kinase C (PKC), and 3.3 microM calcium ionophore (A23187), or 10 microM forskolin (FRK) diminished the cortisol response to PAF, whereas that to ACTH was unaffected. Each of PAF, ACTH, or FRK eliminated the cortisol response to OAG plus A23187, whereas that to FRK was unaffected. These data show that the protein kinase A (PKA)-dependent processes activated by ACTH or FRK can interfere with PAF-induced signal transduction at receptor and post-receptor levels. In contrast, PKC-dependent processes activated by PAF promoted ACTH-signaling at receptor and post-receptor level. Cross-regulation between processes activated by PAF receptor-PKC and by ACTH receptor-PKA might function in the multifactorial regulation of adrenocortical steroidogenesis.