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Biomedical subjects

S Miyabo

Publications and source records attributed to S Miyabo.

At least 127 records · Page 7Linked to original sources

Effect of intrahypothalamic implantation of cortisone acetate on the onset of circadian corticosterone rhythm in neonatal female rats.

Subcutaneous administration of corticosteroids to neonatal rats has been reported to delay the onset of the circadian corticosterone rhythm. Micropellets of a cortisone acetate(CA)-paraffin mixture or paraffin alone were implanted intrahypothalamically or subcutaneously in 2-day-old female rats. 24- or 48-hour patterns of blood corticosterone were obtained serially in individual rats at 21, 28, 35, 56 and 120 days of age. Sham(paraffin)-implanted rats and those bearing CA pellets subcutaneously showed a well-defined circadian corticosterone rhythm at day 28. CA implantation into the anterior hypothalamus, however, caused a delay in the onset of the circadian corticosterone rhythm by 1 week together with a diminished amplitude. In rats with CA pellets in the medial basal hypothalamus, the corticosterone rhythm was not fully established even on day 56, but was evident in most animals on day 120. It is suggested that neonatal CA treatment exerts its effect by inhibiting the maturation of the efferent neural pathways carrying circadian signals from the suprachiasmatic nuclei.

Animals↗

Sexual cyclicity and diurnal corticosterone secretion in rats given hypothalamic transection at two days of age.

Female rats given neural transection between suprachiasmatic and arcuate nuclei at 2 days of age showed regular sexual cyclicity and had ovarian corpora lutea. Thus, the ovarian activity seemed identical to that of intact or sham-operated control rats. However, the diurnal rhythm of the blood corticosterone concentration of the neonatally transected rats was not evident at 22 days of age, while it was already evident in controls. At 30 and 50 days of age, they had clear adrenal rhythms although the peak values were significantly lower than those of controls. Thus, the anterior connections of the medial basal hypothalamus, which are necessary for both cyclic gonadotropin discharge and diurnal corticosterone secretion, are still plastic and not yet established at 2 days of age.

Animals↗

Psychological correlates of stress-induced cortisol and growth hormone releases in neurotic patients.

The mirror drawing test was performed in 23 neurotic patients and plasma cortisol (Fk) and growth hormone (GH) were measured serially throughout the test. The patient's personality was assessed by the Minnesota Multiphastic Personality Inventory and related to the endocrine findings. The results indicated that 1) Fk and GH have different personality correlates; 2) the Fk responders tend to be more "defensive" trying to maintain good "self-control" over inner mental processes; 3) high GH level seems to be associated with personality features such as exaggeration, hostility, and a distorted thinking process; 4) psychoendocrine control mechanisms for Fk and GH tend to offset, rather than enhance, each other.

Adult↗

Prolactin and growth hormone responses to psychological stress in normal and neurotic subjects.

In order to study the response of plasma prolactin (PRL) to acute psychological stress and to compare it with that of growth hormone (GH), the mirror drawing test (MDT) was performed in 20 normal controls (11 male, 9 female) and 22 neurotic patients (12 male, 10 female). Plasma PRL and GH were measured serially before, during and after the test. In controls, the test caused no significant change in plasma levels of either hormone. In neurotic males, the response of PRL to the test was not consistent, whereas, in neurotic females, plasma PRL level rose significantly following the test. Increase of GH, on the other hand, was apparent in the neurotics of both sexes. The correlation between the responses of the two hormones in the neurotics was low and non-significant. The results indicate that although the psychoendocrine coping mechanism in the neurotics works less effectively for both PRL and GH, the two hormones may have different psychological correlates.

Adult↗

[Metabolism of synthetic corticosteroid esters in man (author's transl)].

Metabolism of water-soluble synthetic corticosteroid esters, hydrocortisone hemisuccinate (H-H); hydrocortisone phosphate (HP), prednisolone hemisuccinate (P-H), prednisolone phosphate (P-P), dexamethasone phosphate (D-P) and dexamethasone sulfate (D-S) was studied by i.v. administration of steroids in a dose of 100 mg to 6 healthy volunteers and consequtive urine collections over 24 hrs. Uniary metabolites were separated into free, glucuronide, sulfate and "unhydrolyzed" fractions and measured by means of Porter-Silber (P-S) reaction and isonicotinic acid (INH) reaction. In H-H, H-P and D-S, glucuronide conjugates constituted the largest fraction of P-S positive metabolites in 24 hr-urine. In contrast, P-H, P-P and D-P were excreted mainly as free metabolites. Small but variable portions were found as sulfate and "unhydrolized" conjugates. Time course study revealed that, in H-H, H-P and D-S, the free/glucuronide ratio of P-S positive metabolites decreased progressively or remained low throughout the collection periods, whereas in P-H, P-P and D-P the ratio increased markedly in the 4--12 hr period. For all steroids, the INH/P-S ratio was found to be high in the free fraction and low in the glucuronide fraction; the tendency was especially marked in P-H, P-P and d-p. INH-positive metabolites were also predominant in the sulfate and "unhydrolyzed" fractions. The results indicate that the metabolism of synthetic corticosteroids, in general, is characterized by diminised rate of ring A reduction followed by glucuronide conjugation and compensatory increase in free metabolites, the bulk of which consists of ring A intact, C-20 reduced metabolites. 6-Hydroxylated metabolites may also be increased. Conjugation with sulfuric acid occurs but to a small extent. The consistent presence of "unhydrolyzed" metabolites suggests that portions of esters can be excreted unsplitted. It is also noted that the structure of steroid moieties and type of esters were important factors determining the quantitative and qualitative difference in their metabolic fates.

Dexamethasone↗

Growth hormone and cortisol responses to psychological stress: comparison of normal and neurotic subjects.

The mirror drawing test (MDT) was performed to induce acute psychological stress in 9 normal controls and 10 neurotic subjects. Plasma growth hormone (GH) and cortisol were determined serially before, during, and after the test. In controls the MDT caused no significant change in plasma GH level, while in neurotics plasma GH increased progressively following the test. The increase of cortisol also tended to be greater in neurotics as a group, but there was considerable overlap in individual responses. The maximum increments of GH in neurotics correlated inversely with those of cortisol. The results indicate: 1) effective psychological coping mechanisms operate in normal man to keep the hormonal response minimum. 2) GH response is a more adequate indicator than cortisol response to psychological stress in neurotics. 3) GH and cortisol may have different psychological correlates in neurotics.

Adult↗

Studies on steroid conjugates: IX. Urinary excretion of sulfate conjugated metabolites of cortisol in man.

Following i.v. administration of [4-14C]cortisol, various sulfate conjugated metabolites of cortisol in urine were identified and their respective excretion rates measured. The results obtained demonstrated the following: 1) sulfate conjugates as a group are excreted considerably slower than glucuronide conjugates; 2) sulfate conjugates of steroids with non-reduced ring-A (C-21 sulfates) are excreted (and presumably formed) much faster than steroid-3-sulfates, which require reduction of the ring-A prior to the conjugation; 3) the excretion of C-3 sulfates of ring-A reduced steroids with glycerol side-chain (cortols and cortolones) is significantly faster than those of the corresponding steroids with dihydroxyacetone side-chain (THF, THE and their 5alpha-isomers); 4) the relative concentrations of C-21 sulfates of steroids with ring-A intact (FK, EK, ER, epiER and 6beta-hydroxycortisol) are much higher than the concentrations of C-21 glucuronides of these steroids.

17-Ketosteroids↗

Corticosteroids in human blood. VIII. Cortisol metabolites in plasma of normotensive subjects and patients with essential hypertension.

Results of our previous studies revealed a derangement in the peripheral metabolism of adrenal steroids in patients with essential hypertension. To investigate further this finding, all indIVidual free and conjugated metabolites of cortisol were isolated, identified and quantitated in plasma of 14 normotensive subjects and 13 patients with benign, uncomplicated essential hypertension, following iv administration of a tracer dose of [4-14-C] cortisol. In addition, plasma levels of endogenous cortisol were determined at 8 AM and 4 PM in all the subjects examined. The results obtained revealed the following statistically significant differences between normotensives and hypertensives: 1) Mean plasma concentrations of cortisol metabolites reduced in ring-A with nonreduced 20-ketone, tetrahydrocortisol, tetrahydrocortisone, and their 5alpha-epimers, were 30% lower in the hypertensives; since these steroids constitute the bulk of the major group of cortisol metabolites--the glucuronide conjugates, plasma levels of this group of conjugates measured in toto were also found to be significantly lower in the hypertensives. 2) Concentrations of cortisol metabolites with non-reduced ring-A (delta-4-3-keto configuration preserved) but with reduced 20-ketone and/or hydroxylated at C-6, 20alpha- and 20beta- dihydrocortisol, 6alpha- and 6beta-hydroxycortisol, and 6-hydroxy-20-dihydrocortisol (all 4 isomers), were 73%, 48% and 68% respectively, higher in the hypertensives; since these steroids constitute the bulk of the sulfate-conjugated and nucleoside-complexed metabolites of cortisol, plasma levels of these groups of metabolites, measured in toto, were also found to be higher in the hypertensives. No significant difference was found between normotensives and hypertensives in the AM and PM plasma levels of cortisol. These findings, in conjunction with the results of our studies on urinary corticosteroid metabolites, which yielded identical findings, provide evidence for a decreased activity of hepatic cortisol-delta-4-hydrogenase enzyme system and increased activities (presumably compensatorily) of cortisol-20-reductase and 6-hydroxylase enzyme systems in patients with essential hypertension. The interrelation of these findings with those of other investigators studying steroid metabolites in hypertension, points to the corticosteroid metabolizing enzymes may be an etiological factor in essential hypertension.

Adult↗