Showing papers on "Adrenal cortex published in 1975"

Inhibition of replication of normal adrenocortical cells in culture by adrenocorticotropin.

Abstract: Adrenocorticotropic hormone (ACTH) inhibited [3H]thymidine incorporation in normal adrenocortical cells of adult rats in culture, with a concomitant increase in corticosterone production and a characteristic retraction of cells. Both dibutyryl cyclic AMP and an analog of ACTH, which produces virtually no cyclic AMP, inhibited DNA synthesis and stimulated steroid production. ACTH inhibited the proliferation of adrenocortical cells obtained from suckling rats as well as the cells obtained from the capsular tissue of adult rat adrenal glands, whereas insulin caused a stimulation of DNA synthesis. These results suggest that the major role of ACTH is to induce the transformation of the undifferentiated cells of the adrenal gland into functional fasciculata cells and that the proliferation of adrenocortical cells may be under control of factors other than ACTH.

Ornithine decarboxylase activity: control by cyclic nucleotides.

Abstract: Both exposure to cold and administration of aminophylline result in rapid increases in cyclic adenosine monophosphate (cyclic AMP) in the adrenal medulla and adrenal cortex. These increases are followed by dramatic increases in ornithine decarboxylase activity is due to new enzyme systhesis. The data suggest that the decarboxylase activity is regulated by an increase in cyclic AMP.

Aldosterone Production by Isolated Adrenal Glomenilosa Cells: Stimulation by Physiological Concentrations of Angiotensin II

Abstract: The production of aldosterone by isolated canine zona glomenilosa cells was measured after the incubation of cell suspensions with angiotensin II and ACTH, and during changes in extracellular potassium concentration. Adrenal cell suspensions were prepared by collagenase digestion and physical dispersion of the capsular layer of the dog adrenal cortex, and aldosterone production was determined by direct radioimmunoassay of cell incubation media. The isolated dog adrenal cells were highly responsive to angiotensin II, with aldosterone production significantly stimulated by concentrations of the octapeptide as low as 10-11M. Thus, the steroidogenic response of zona glomenilosa cells was consistently observed at peptide concentrations within the physiological range of angiotensin II in dog plasma, i.e., 2.0–5.0 × 5.0 × 10-11M. The maximum aldosterone response of 3–8 times the basal level of steroid production was induced by 3 × 10-10M angiotensin II, and a decrease in aldosterone production occurred at peptid...

Intercellular communication in the rat anterior pituitary gland. An in vivo and in vitro study.

Abstract: The concept of "stimulus-secretion coupling" suggested by Douglas and co-workers to explain the events related to monamine discharge by the adrenal medulla (5, 7) may be applied to other endocrine tissues, such as adrenal cortex (36), pancreatic islets (4), and magnocellular hypothalamic neurons (6), which exhibit a similar ion-dependent process of hormone elaboration. In addition, they share another feature, that of joining neighbor cells via membrane junctions (12, 26, and Fletcher, unpublished observation). Given this, and the reports that hormone secretion by the pars distalis also involves a secretagogue-induced decrease in membrane bioelectric potential accompanied by a rise in cellular [Ca++] (27, 34, 41), it was appropriate to test the possibility that cells of the anterior pituitary gland are united by junctions.

Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle

Abstract: In order to assess the ovarian and adrenal contribution to peripheral levels of testosterone (T), 5α-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) in premenopausal women, six normally menstruating subjects were studied during two complete mentrual cycles. The first cycle served as control and dexamethasone was given during the second cycle. Plasma cortisol (F) was measured to assess the degree of adrenal suppression. Plasma progesterone (P), 17-hydroxyprogesterone (17-P) and estradiol-17β (E2) served as indirect indices of ovulation. The estimation of plasma LH located the midcycle peak and the data for all steroids were evaluated in relation to the LH peak. All cycles studied were apparently ovulatory, as judged by the plasma levels of P, 17-P and E2. Dexamethasone treatment had no detectable effect on the levels of these three steroids. Assuming that dexamethasone suppressed completely the adrenal cortex and had no detectable effect on ov...

Studies on the binding of 125I-labelled corticotrophin to isolated rat adrenocortical cells.

Abstract: Isolated adrenocortical cells, prepared by collagenase disaggregation of normal rat adrenal glands, have been used to study the binding characteristics of 125I-labelled corticotrophin (ACTH) of established biological activity. The binding of the labelled hormone to these whole cells was highly specific, only peptides possessing steroidogenic activity displaced the labelled hormone. Binding was rapid, being complete within 5 min of adding the hormone, and the amount of hormone bound remained constant for up to 20 min thereafter. Over the range 160-10000pg ACTH/ml, increased binding of the hormone was observed at all concentrations of hormone which stimulated steroidogenesis. However at levels of ACTH which stimulated maximal steroidogenesis there was no saturation of binding. This provides the first direct evidence for the existence of 'spare receptors' for ACTH on whole adrenocortical cells. Scatchard analysis of the binding data suggests that there are two types of receptor for ACTH in this preparation of cells. One receptor is of high affinity (dissociation constant equals 2-5 times 10-10 mol/l) with about 3000 sites/cell and the other is of lower affinity (dissociation constant equals 1 times 10-8 mol/l) with about 30000 sites/cell.

Circadian rhythm of tyrosine hydroxylase induction by short-term cold stress: modulatory action of glucocorticoids in newborn and adult rats.

Abstract: The trans-synaptic induction of tyrosine hydroxylase [tyrosine 3-monooxygenase; EC 1.14.16.2, L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating)] in adrenal medulla and sympathetic ganglia by short-term (1-2 hr) cold stress (4 degrees) exhibits a circadian rhythm which seems to be causally related to the diurnal changes in adrenal glucocorticoid synthesis. In induction is maximal during the morning hours, when plasma corticoid concentrations (reflecting corticoid synthesis in the adrenal cortex) are minimal. In contrast, initiation of tyrosine hydroxylase induction in sympathetic ganglia is only possible in the afternoon. These observations suggest that tyrosine hydroxylase inducibility in the adrenal medulla is optimal during periods of low corticoid synthesis (the adrenal medulla is exposed to excessively high corticoid concentrations directly originating from the adjacent cortex), whereas in sympathetic ganglia an induction is only possible during the period of high plasma corticoid concentrations. This assumption is supported by the observation that in the first postnatal weeks, when the pituitary--adrenocortical system is not yet operating and plasma corticoid concentrations are low, initiation of tyrosine hydroxylase induction in the adrenal medulla is possible at any time of the day, whereas in sympathetic ganglia it is not possible at all. However, after administration of glycocorticoids initiation of tyrosine hydroxylase induction by short-term cold stress is also possible in newborn animals and in adults during the morning hours. The importance of glucocorticoids as modulators for the initiation of trans-synaptic tyrosine hydroxylase induction can also be deduced from the observation that in sympathetic ganglia kept in organ cultures and induction of the hydroxylase by cholinomimetics is only possible when glycocorticoids are added to the culture medium.

Effect of prolonged low-dose angiotensin II infusion on the sensitivity of adrenal cortex in man.

Abstract: The effect of incremental infusions of isoleucine-5-angiotensin II on blood pressure and plasma aldosterone concentrations was studied in normal man before and after 66 hours of intravenous infusion of angiotensin II at 2 ng kg-1 min-1, sodium and potassium balance being kept roughly constant throughout. Plasma sodium and ACTH concentrations were unaltered, but plasma potassium and magnesium levels and basal plasma cortisol fell slightly after prolonged angiotensin administration. During the prolonged angiotensin infusion plasma renin activity was suppressed, and there was a sustained elevation of arterial pressure and plasma aldosterone concentration. Aldosterone excretion, while clearly increased, showed a regular circadian rhythm, with peak values in the early morning. The angiotensin II-pressor relationship was not significantly changed after the prolonged infusion of angiotensin II, while the angiotensin II-aldosterone dose-response curve was steeper than in the basal state but not identical with that of sodium depletion. No differences were observed in the pressor or aldosterone-stimulant effects of the isoleucine-5 and valine-5 forms of angiotensin II. A trophic effect of angiotensin II on the adrenal cortex may provide a partial explanation for the enhanced response of aldosterone to angiotensin II in sodium depleted man.

Synthesis and evaluation of (Des-Asp1)angiotensin I as a precursor for (Des-Asp1)angiotensin II ("Angiotensin III").

Abstract: The nonapeptide [des-Asp1]angiotensin I (IV), synthesized by Merrifield's solid-phase procedure, was tested as a possible substrate for the converting enzymes from porcine lung and plasma. IV, [des-Asp1]angiotensin II (III), [des-(Asp1,Arg2)]angiotensin II (V), [des-(Asp1,Arg2,Val3)]angiotensin II (VI), [Sar1,Ile8]angiotensin II (VII), and [des-Asp1,Ile8]angiotensin II (VIII) possessed 0.5, 20, 2, 0 less than 0.1, and less than 0.01% of the inotropic activity (rabbit atria), 1, 15, 5, 0, 3, and 0% secretory activity of the cat adrenal medulla, and 0.0, 150, 0.5, 3, and 10% of the adrenal steroidogenic activity of angiotensin II, respectively. When tested for their antagonistic activity in the above tissues, only VII and VIII were found to inhibit responses to angiotensin II. The pA2 values for VII and VIII were 8.31 and 10.0 in the adrenal cortex and 9.31 and 9.16 in the adrenal medulla, respectively. All these peptides were also tested as product inhibitors for the plasma and lung converting enzymes. With the plasma enzyme, the ID50 values were II, 1.6 X 10(-4) M; III, 5 X 10(-5) M; V, 1.2 X 10(-4) M; VI 5 X 10(-4) M; VII 5 X 10(-5) M; VIII, 5 X 10(-4) M. Thus, IV is a good substrate for converting enzymes from lung and plasma while all other compounds were inhibitors of these enzymes. The most potent inhibitors of converting enzyme were III followed by VII and VIII. With the exception of II and III, all the other analogs had very low intrinsic activities, per se. These results suggest (a) an alternate pathway for the formation of heptapeptide III, viz., by the action of converting enzyme on the nonapeptide IV, and (b) that III may also be acting as inhibitor of the converting enzyme by the feedback mechanism.

Apparent modification of a specific component of the acth-binding site

Abstract: A B S T R A C T The failure of certain adrenal tumors to respond to ACTH was investigated in vivo by administration of corticotropin- ( 1-24) -tetracosapeptide (ACTH1-2) and dexamethasone and in vitro by studying the binding properties of ACTH1-2 and prostaglandin E1 (PGE1) and their effect on adenylate cyclase activity of the tumors' crude membranes; in addition, in five cases the stimulation of cortisol production in isolated adrenal cells by both hormones and dibutyryl cyclic adenosine 3',5'-monophosphate (cAMP) was also studied. The results obtained in 13 hormone-producing tumors of the human adrenal cortex, i.e. 10 carcinomas and 3 adenomas, were compared with those found in normal human adrenal glands. According to the adenylate cyclase responses to ACTH1- and PGE1, the tumors fall into different categories. In the first group are six tumors in which the adenylate cyclase was stimulated by both ACTHl-2X and PGE1; in addition specific binding could be demonstrated for the two hormones in all six. The binding affinity for 'I-ACTH1-2 was found to be about 10 times higher than that for 'I-ACTHu-24. In the one tumor in which the experiment was performed, bound 'IACTH1-X was displaced by ACTH1-1o. These results are similar to the ones found in normal human adrenal preparations. For two tumors of the group in which ACTH did not increase steroidogenesis in vivo, the biochemical abnormality might be located beyond cAMP formation.

Nicotine-induced stimulation of steroidogenesis in adrenocortical cells of the cat.

Abstract: 1. The effect of nicotine on steroid production and release from trypsin-dispersed cat adrenocortical cells was investigated. 2. Nicotine, like adrenocorticotrophin (ACTH), elicited a dose-dependent increase in steroidogenesis, which depended upon the presence of calcium in the medium. 3. Augmented steroid production evoked by submaximal concentrations of ACTH monobutyryl cyclic adenosine 3',5'-monophosphate (AMP), or prostaglandin E2 was further enhanced by steroidogenic concentrations of nicotine. 4. These results are discussed in relation to the possible mode of action of nicotine on cortical cells and to the potential consequences of smoking during stress.

ACTH and prostaglandin receptors in human adrenocortical tumors. Apparent modification of a specific component of the ACTH-binding site.

Abstract: The failure of certain adrenal tumors to respond to ACTH was investigated in vivo be administration of corticotropin-(1-24)-tetracosapeptide (ACTH1-24) and dexamethasone and in vitro by studying the binding properties of ACTH1-24 and prostaglandin E1 (PGE1) and their effect on adenylate cyclase activity of the tumors' crude membranes; in addition, in five cases the stimulation of cortisol production in isolated adrenal cells by both hormones and dibuttyryl cyclic adenosine 3',5'-monophosphate (cAMP) was also studied. The results obtained in 13 hormone-producing tumors of the human adrenal cortex, i.e. 10 carcinomas and 3 adenomas, were compared with those found in normal human adrenal glands. According to the adenylate cyclase responses to ACTH1-24 and PGE1, the tumors fall into different categories. In the first group are six rumors in which the adenylate cyclase was stimulated by both ACTH1-24 and PGE; in addition specific binding could be demonstrated for the two hormones in all six. The binding affinity for 125I-ACTH1-24 was found to be about 10 times higher than that for 125I-ACTH11-24. In the one tumor in which the experiment was performed, bound 125I-ACTH1-24 was displaced by ACTH1-10. These results are similar to the ones found in normal human adrenal preparations. For two rumors of the group in which ACTH did not increase steroidogenesis in vivo, the biochemical abnormality might be located beyond cAMP formation. A second group encompasses six tumors in which the steroidogenesis in vivo and the adenylate cyclase activity were insensitive to ACTH1-24 but in which the enzyme was stimulated by PGE1 and NaF. However, these preparations bound 125I-ACTH1-24 and 125I-ACTH11-24, the binding affinity being similar for both peptides but 10 times lower than the one found in normal adrenal cortex for 125I-ACTH1-24. In the only case of this group where it was tested, ACTH1-10 did not displace bound 125I-ACTH1-24. This result strongly suggests the possibility of a modification or a loss of the receptor site that binds the N-terminal sequency (1-10) of ACTH, the biologically active part of the molecule. In the last tumor, both PGE1 and ACTH were unable to stimulate adenylate cyclase activity and steroid production in a preparation of isolated adrenal cells, although steroidogenesis was stimulated by dibutyryl though steroidogenesis was stimulated by dibutyryl cAMP. No specific binding for PGE1 could be demonstrated. However, 125I-ACTH1-24 and 125I-ACTH11-24 were found to be bound to the tumor with the same affinity.

Kidney and adrenocortical hormones.

Abstract: We have presented a review of the interrelationship between the kidney and the adrenocortical steroids, aldosterone and cortisol primarily in the regulation of water and electrolyte metabolism. The presentation is divided into three parts: (1) the influence of cortisol and aldosterone on renal structure and function; (2) the effect of kidney disease on secretion and metabolism of these steroids, and (3) the role of the kidneys in the plasma clearance of these steroids and their metabolites. There is no evidence that an excess or deficit of these steroids have a direct effect on renal structure, but both are necessary to maintain normal GFR and RPF. Glucocorticoids augment renal hemodynamics in pharmacologic doses. The phenomenon of 'escape' by the kidney from the sodium-retaining effect of adrenocortical steroids is discussed in detail, as well as the ability of glucocorticoid to antagonize the sodium retaining activity of any adrenal steroid of analogue with lesser glucocorticoid noperties. It is included that the impaired water dunesis of glycocorticoid deficiency is due to the absence of the permissive action of these steroids on the kidney, augmented at times by enhanced ADH secretion in response to sustained nonosmotic stimuli. The effect of gluco and mineralocorticoids on the renal excretion of divalentions and uric acid is also discussed. While progressive chronic renal failure (CRF) does not seem to significantly after the secretion or metabolism of cortisol it is possible that CRF causes a state of chronic hyperaldosteronism that is essential to maintain normal excretion (secretion) of potassium per nephron as renal mass progressively decreases. A direct or an indirect effect of potassium ion may be responsible for the hypersecretion or aldosterone rather than the renin-angiotensin system.

Investigations on the turnover of adrenocortical mitochondria

Abstract: The effects of chronic administration of dexamethasone (for up to 15 consecutive days) on both the morphology and DNA-synthesis of the mitochondria of the rat adrenal zona fasciculata were investigated by stereologic and autoradiographic techniques. Up to the 3rd day of continuous dexamethasone treatment, the average volume of mitochondria did not change, whereas the number of mitochondria per cell was significantly decreased. From the 3rd to the 15th day of hormonal administration both the volume and number of mitochondria were found to decrease in proportion to the duration of treatment. Autoradiography showed that after the 3rd day of dexamethasone administration there is virtually no incorporation of 3H-thymidine into the mitochondrial compartment. These findings are discussed in the light of evidence indicating that dexamethasone blocks ACTH-release by inhibiting the hypothalamo-hypophyseal axis. The results confirm the view that ACTH controls the maintenance of growth and proliferation of rat adrenocortical mitochondria.

Action of [1-des(aspartic acid), 8-isoleucine] angiotensin ii upon the pressor and steroidogenic activity of angiotensin ii.

Abstract: The vascular and steroidogenic responses to [1-Sarcosine, 8-Isoleucine]-, and to [1-Des(Aspartic acid), 8-Isoleucine] angiotensin II were compared in bilaterally nephrectomized, ACTH-suppressed dogs receiving constant infusions of angiotensin II. Aldosterone secretion rate was significantly inhibited by pretreatment with 200 ng/Kg/min of the heptapeptide, [1-Des(Aspartic acid), 8-Isoleucine] ang II, but not by similar doses of the octapeptide, [1-Sarcosine, 8-Isoleucine] ang II. In contrast, the pressor action of ang II was unaffected by [1-Des(Aspartic acid), 8-Isoleucine] ang II though significant inhibition occurred with relatively small doses of [1-Sarcosine, 8-Isoleucine] ang II. This study suggests that: (a) angiotensin receptors in adrenal cortex and vascular smooth muscle are functionally different, and (b) [1-Des(Aspartic acid), 8-Isoleucine] angiotensin II is a specific antagonist of steroidogenic effect of ang II.

Potentiation of adrenocortical response upon intermittent stimulation with corticotropin in normal subjects.

Abstract: Modifications of adrenocortical steroidogenic response to ACTH as a consequence of acute prior exposure to this hormone, were studied in 106 normal subjects divided in 15 experimental groups. Adrenocortical response was assessed by the changes in plasma cortisol level and in urinary excretion of cortisol, 17-ketogenic and 17-ketosteroids; in some experiments plasma 11-deoxycortisol, corticosterone, progesterone and 17-hydroxyprogesterone were determined as well, together with urinary excretion of the unconjugated form of 11-deoxycortisol and corticosterone. Slow (8-h) intravenous administration of ACTH in amounts producing maximal response, leaves the adrenal cortex in a hyperresponsive state in case of further stimulation for up to 3 days, while the adrenocortical secretion comes back to baseline in the meantime. This potentiation phenomenon seems to concern essentially cortisol secretion since, among the compounds measured only cortisol and 11-deoxycortisol secretions in creased progressively in amplitu...

Vascular and adrenocortical responses to a specific antagonist of angiotensin II.

Abstract: Angiotensin II receptors in vascular smooth muscle and adrenal cortex have been characterized in the dog. The evidence was derived chiefly from experiments that assessed the ability of a structural analog of angiotensin II, [Sar1, Ile8] AII, to antagonize the effects of exogenously administered angiotensin II on arterial pressure and aldosterone secretion. [Sar1, Ile8] AII is a potent and specific blocker of the pressor response to angiotensinII; in the adrenal cortex, it is a much less effective inhibitor of aldosterone biosynthesis. These results indicate differences in the receptor sites for angiotensin II in vascular smooth muscle and adrenal cortex. Further, they raise the possibility that angiotensin II stimulates aldosterone secretion by mechanisms other than have already been proposed.

Bovine adrenal cortex adenylate cyclase: properties of the particulate enzyme and effects of guanyl nucleotides.

Abstract: The preparation of a partially purified plasma membrane fraction from bovine adrenal cortex is described. Adenylate cyclase in this particulate preparation retained high sensitivity to ACTH and is also stimulated by 5′-guanylyl-imidodiphosphate [Gpp(NH)p]. GTP, in contrast to Gpp(NH)p, had very little intrinsic activity to stimulate adenylate cyclase. GTP could however, with high affinity, inhibit the Gpp(NH)p effects on adenylate cyclase. When the concentration of creatine phosphate, a component of the ATP-regenerating system in the adenylate cyclase assay mixture, was lowered from 20 to 2 mM (at 0.1 mM ATP, 5 mM Mg2+) GTP, dGTP and other nucleotides like ITP and much less UTP or CTP gained considerable intrinsic activity in the presence of ACTH to stimulate adenylate cyclase. The apparent affinities of the nucleotides for ACTH-stimulated adenylate cyclase from bovine adrenal cortex (at 2 mM creatine phosphate) were, GTP=dGTP>Gpp(NH)p>Gpp(CH2)p (5′-guanylyl-β, γ-methylene-diphosphonate) >ITP>UTP>CTP. These findings indicate that regulatory nucleotide binding sites exist for bovine adrenal cortex adenylate cyclase. Their specificity is similar to the nucleotide sites modulating angiotensin binding in bovine adrenal cortex plasma membranes (Glossmann et al., 1974a). The regulatory nucleotide binding sites for the adrenal cortex adenylate cyclase complex can also be identified under conditions where only Gpp(NH)p has high intrinsic activity (e.g. at 20 mM creatine phosphate) but other nucleotides like GTP act as antagonists. Both stimulants, ACTH and Gpp(NH)p, appear to remain firmly bound to the particulate membrane preparation, as suggested by preincubation experiments.

Competitive binding activity of angiotensin II analogues in an adrenal cortex radioligand-receptor assay;.

Abstract: The competitive binding activities of a number of angiotensin analogues were determined in a radioligand-receptor assay employing bovine adrenal crotex homogenate and [125I] iodoangiotensin II. This assay system has been shown to provide a precise and convenient method for evaluation and comparison of the binding-inhibition potencies of angiotensin II derivatives with agonist and antagonist activities. Agonist analogues of angiotensin II showed competitive binding activities in proportion to their known biological activities upon aldosterone production by the adrenal zona glomerulosa. Thus, the [Des-Asp1] heptapeptide of angiotensin II was equipotent with the native octapeptide in terms of binding-inhibition activity, and the [Sar1] derivative of angiotensin II was more potent than the native peptide. By contrast, the [Des-Asp1, Des-Arg2] hexapeptide and the [Des-Phe8] heptapeptide showed less than 1% of the activity of angiotensin II. Angiotensin II antagonists formed by C-terminal substitution of the octapeptide with isoleucine or alanine were also found to exhibit binding-inhibition activities in proportion to their known potencies as antagonists of the action of angiotensin II upon smooth muscle. Certain antagonists, such as [1-guanidoacetic, 8-isoleucine]-angiotensin II and [1-sarcosine, 8-isoleucine]-angiotensin II displayed significantly greater binding-inhibition potency than E1Asp1, Ileu5,-angiotensin II in the adrenal receptor system. Several, such as [Sar1, Ala8]-angiotensin II and [MeAla1, Ileu8]-antiotensin II were approximately equipotent with angiotensin II, while others such as [1-succinic acid, 8-alanine]-angiotensin II and [D-Ileu8]-angiotensin II showed no significant binding-inhibition activity. The relative binding-inhibition potencies of the antagonist peptides showed a general correlation with the pA2 values of the same components determined upon the smooth muscle response of the isolated aortic strip. The binding-inhibition potency of angiotensin II antagonists was also strongly influenced by the charge of the N-terminal residue, with enhancement of activity by more basic substituents and abolition of activity by highly acidic residues. The influence of the basicity of the N-terminus upon receptor binding was also observed with the agonist analogue [Sar1]-angiotensin II, which showed a 2- to 3-fold increase in binding-inhibition potency in comparison to native angiotensin II. The significant enhancement of binding-inhibition potency by N-terminal sarcosine substitution is attributable to higher affinity of the modified peptide for the angiotensin II receptor site, and is consistent with the increased activity of [Sar1]-angiotensin II upon smooth muscle and aldosterone production in vitro. The determination of binding-inhibition activity in the adrenal radioligand receptor assay provides a valid and convenient method for analysis of the role of binding affinity in the actions of competitive antagonists upon the responses of target cells to angiotensin II.

The Hippocampus and Regulation of the Hypothalamic-Hypophyseal-Adrenal Cortical Axis

Abstract: It has been established since 1950 that the hormones of the adrenal cortex are regulated by the central nervous system. The adrenal cortex is stimulated by adrenocorticotropic hormone (ACTH) carried through the circulatory system from the adenohypophysis, which is activated by corticotropin releasing factor (CRF) brought via the hypophyseal portal vessels from the median eminence of the hypothalamus. Many structures of the limbic system project to the hypothalamus and are therefore potential candidates for modulating adrenocortical hormone secretion. The hippocampus has been implicated in such a role since the late 1950s. The results of much of the research in this area have led many authors to conclude that the hippocampus inhibits hypothalamic mechanisms controlling the secretion of adrenal corticosteroid hormones. However, a close examination of the existing data reveals that this generalization is probably misleading oversimplification since (1) there is more than one functional system which has access to the final common path of adrenocortical steroid hormone secretion and (2) different methods of hippocampal disruption give results which lead to different conclusions about its function. In this chapter, the data relating to the role of the hippocampus in the regulation of this hormone system will be critically analyzed using these two points as an organizational framework.

Synthesis of a new adrenal cortex imaging agent 6β-131 I-iodomethyl-19-nor cholest -5(10)-en-3β-ol (NP-59)

Abstract: A new adrenal cortex imaging agent. 6β-131 I-iodomethyl-19-norcholest-5(10)-en-3β-ol (NP-59)[I] was synthesized by the homallylic rearrangement of 19-iodocholesterol or directly from cholest-5-ene-3β, 19-diol-19-toluene-p-sulfonate via homoallylic rearrangement with the iodide ion as a nucleophile and subsequent exchange with Na131I. NP-59 appears to concentrate 5 times better than 19-iodocholesterol in the rat adrenal and is currently being evaluated as a possible diagnostic agent in man.

Steroid Hydroxylations by Human Adrenal Cortex Microsomes1,2

Abstract: Microsomes were prepared from human adrenals obtained at the time of cadaveric renal transplantation Microsomes were assayed for cytochrome P-450 concentrations (mean =063 nmol/mg protein) and NADPH-cytochrome c reductase activity (mean 65 nmol times min-1 times mg-1 protein) Rates of steroid hydroxylation were measured In man, the rate of 21-hydroxylation of 17-hydroxyprogesterone was approximately three times the rate of 21-hydroxylation of progesterone The rate of 17-hydroxylation of progesterone was approximately three times the rate of 21-hydroxylation of progesterone Substrate binding to microsomes showed a type I spectrum with progesterone and 17-hydroxy-progesterone Both substrates bound all spectrally identifiable sites Antibody prepared against procine NADPH-cytochrome c reductase inhibited concomitantly human reductase, 21-hydroxylation of progesterone and 17-hydroxyprogesterone, and 17-hydroxylation of progesterone These results were compared to previous studies with beef adrenal microsomes No specific evidence was obtained to suggest multiple forms of 21-hydroxylase in human adrenal microsomes It appears as though the human adrenal microsomal cytochrome P-450 electron transport chain is immunologically similar to those studied previously--beef adrenal, and rat and human liver

Relation of intracellular K+ and steroidogenesis in isolated adrenal zona glomerulosa and fasciculata cells.

Abstract: 1. Intracellular K + content, water spaces and corticosterone output were measured in isolated zona glomerulosa and zona fasciculata-reticularis cell suspensions of rat adrenal cortex, after incubations in vitro under conditions designed to alter steroidogenesis. 2. Intracellular K + of unpurified zona glomerulosa cells was not altered after stimulation of corticosterone output with serotonin. Similarly, with zona glomerulosa cells purified by unit gravity sedimentation, no change in intracellular K + was detected after stimulation of steroidogenesis with serotonin or angiotensin II. 3. In high-potassium medium (final concentration 84 mmol/l), parallel increases in intracellular K + and corticosterone output were observed with both unpurified and purified zona glomerulosa cells. However, a similar increase in intracellular K + also occurred in high-potassium medium with zona fasciculata cells, whose steroid output is unresponsive to external potassium concentration ([K + ]). 4. Ouabain at 10 −5 mol/l depressed the intracellular [K + ] of glomerulosa cells but did not alter basal or stimulated corticosterone output. Similar results were obtained with fasciculata cells. 5. Ouabain at 5×10 −4 mol/l further depressed intracellular [K + ] of glomerulosa cells and inhibited basal and stimulated corticosterone output. However, this concentration of ouabain also inhibited steroidogenesis in fasciculata cells. 6. These results demonstrate a variety of situations where changes in intracellular [K + ] are dissociated from those in corticosterone output and indicate that intracellular [K + ] cannot be the sole mechanism regulating steroidogenesis under these conditions.