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Biomedical subjects

J Herbert

Publications and source records attributed to J Herbert.

At least 199 records · Page 11Linked to original sources
PubMed1985

The passage of 5 alpha-dihydrotestosterone from serum into cerebrospinal fluid and LH negative feedback in castrated rhesus monkeys.

Seven castrated monkeys were given either 50 or 100 micrograms 5 alpha-dihydrotestosterone (DHT) propionate/kg per day. There was no correlation between serum and cerebrospinal fluid (CSF) levels of DHT, which remained very low in the CSF (0.3-0.6% of blood levels) despite the presence of high, supraphysiological amounts in the circulation. There was also no relation between unbound DHT in the blood and the CSF, in which all DHT is unbound. These results differ from previous work on testosterone, the metabolic precursor of DHT. 5 alpha-Dihydrotestosterone propionate at the higher dose maintained suppressed levels of serum LH; LH in two out of four monkeys treated at the lower dose increased to levels observed in castrated, untreated rhesus monkeys. There was no predictable relationship between the amount of DHT in the CSF and levels of LH in the blood: by contrast, DHT in the blood was correlated with serum levels of LH. Levels of LH rose in monkeys in which total blood DHT fell below about 68 nmol/l and, even more obviously, if unbound DHT decreased to less than about 2 nmol/l. Differences between the distribution of testosterone and DHT between blood and CSF cannot be explained by serum binding, lipid solubility or clearance from the brain, and suggest that there may be some mechanism for excluding DHT from the CSF. Though DHT reaches the CSF from the blood in small amounts, levels there do not relate predictably to those in the vascular compartment. It seems unlikely, therefore, that levels of intracerebral DHT are controlled by changes in those of the blood.

Animals↗
PubMed1985

Relationship between adrenocorticotrophin bioactivity in blood and cerebrospinal fluid of rhesus monkeys.

Adrenocorticotrophin levels, measured by a cytochemical bioassay, were determined in the plasma and cerebrospinal fluid (CSF) of adult female rhesus monkeys which were ovariectomized and receiving oestrogen replacement therapy. In control monkeys, ACTH bioactivity was found in both CSF (10.2 +/- 1.8 ng/l) and plasma (186 +/- 51 ng/l) in samples taken at 14.00 h (lights on: 07.00-19.00 h). Dexamethasone treatment (0.2 mg/kg) twice daily for 4 days suppressed plasma ACTH levels (52.8 +/- 25.2 ng/l) but had no effect on CSF levels (7.6 +/- 2.7 ng/l). Raising plasma ACTH, either by daily injections of a long-acting preparation of ACTH (1-24) for 6 days or by bilateral adrenalectomy (and subsequently with-drawing cortisol replacement therapy) also resulted in no detectable changes in ACTH levels in the CSF. A regression analysis between ACTH in the plasma and CSF from samples taken throughout the experiments showed no correlation. In contrast, measurement of ACTH by radioimmunoassay, whilst satisfactory for determination of this peptide in plasma, could not identify authentic ACTH in the CSF. It is concluded that bioactive ACTH does not enter the CSF in detectable quantities from either the peripheral vascular compartment or from the animal's own pituitary gland, and that reducing ACTH secretion from the pituitary also has no effect on levels of ACTH in the CSF. This is in marked contrast to other pituitary peptide hormones, including prolactin, which is secreted together with ACTH during 'stress' but which, unlike ACTH, enters the CSF relatively easily.

Adrenalectomy↗
PubMed1985

Naloxone-induced secretion of LH in the male Syrian hamster: modulation by photoperiod and gonadal steroids.

The role of endogenous opiates in the regulation of photoperiodically induced testicular regression was studied in the male Syrian hamster. In reproductively active hamsters exposed to a long photoperiod (LD; 16 h light: 8 h darkness) or to short days (SD; 8 h light: 16 h darkness) for 20 weeks or to SD after pinealectomy, administration of naloxone, a competitive opiate receptor antagonist, at doses of 2.5-20 mg/kg, significantly increased serum LH concentrations. In marked contrast, these doses of naloxone did not produce any change in LH levels in reproductively quiescent hamsters exposed to SD for 8 weeks. The influence of gonadal steroids on the LH response to naloxone was studied in hamsters castrated or castrated and implanted s.c with a capsule containing testosterone. Naloxone did not induce LH release in castrated hamsters maintained in LD or in SD, but this response was restored in LD but not SD when serum testosterone concentrations were maintained at levels similar to those observed in intact reproductively active hamsters. These results show that inhibition of reproduction by the photoperiod prevents naloxone-induced LH release in the male hamster. This lack of response to naloxone is not due, however, to the lower testosterone titres present in these animals compared with reproductively active animals. Responsiveness to naloxone can be restored when the animal is rendered insensitive to the inhibitory photoperiod either by removal of the pineal gland or by induction of photorefractoriness by extended exposure to SD.

Animals↗
PubMed1985

Dissociation between emotional and endocrine responses preceding an academic examination in male medical students.

A study was made in 2 consecutive years of the emotional states and morning and afternoon serum levels of prolactin, cortisol and testosterone of male medical students during a 4- to 5-week period preceding a major university examination. 'Distress', 'anxiety' and, to a lesser degree, 'depression' increased during the 2 weeks immediately preceding the examination and were positively correlated with personality anxiety or neuroticism traits. Group means for hormones showed no consistent change over the same period. Neither was there evidence for a correlation between endocrine and emotional changes within individual students during the pre-examination period. A restricted study showed that there were significant increments in cortisol in samples taken during the examination itself. Changes in emotional state before an examination occurred in the absence of equally dramatic changes in levels of the three hormones studied, though this relationship may have altered during the examination itself. This suggests that the factors controlling the two categories of response may relate differently, in some way, to the imminence of this stressful event.

Adult↗
PubMed1984

Rabbit and rat C-reactive proteins bind apolipoprotein B-containing lipoproteins.

Immobilized rabbit and rat C-reactive protein (CRP) were found to selectively bind apolipoprotein B (apoB)-containing lipoproteins (low density lipoprotein, LDL and very low density lipoprotein, VLDL) from whole serum in a manner similar to that previously reported with human CRP. In acute phase human serum the CRP is in a free form, not complexed with lipoprotein or any other macromolecular ligand, and in acute phase serum from most rabbits fed on a normal diet the rabbit CRP was also free. However, in acute phase serum or heparinized plasma from hypercholesterolemic rabbits part or all of the CRP was found by gel filtration and immunoelectrophoretic techniques to be complexed with beta-VLDL, an abnormal apoB-containing plasma lipoprotein present in these animals. The presence of extent in different serum samples of CRP complexed with lipoprotein correlated closely with the serum apoB concentration. The formation of complexes between native, unaggregated rabbit CRP in solution and apoB-containing lipoproteins was readily demonstrable experimentally both with the isolated proteins and in whole serum. In all cases these interactions were calcium-dependent and inhibitable by free phosphoryl choline. The present findings extend earlier work in man and the rabbit and indicate that among the C-reactive proteins from different species, which are structurally highly conserved, the capacity for selective binding to apoB-containing plasma lipoproteins is also a constant feature. These interactions may therefore be related to the in vivo function of CRP in all species and this function may in turn be relevant to pathological conditions, such as atherosclerosis, in which lipoproteins are important.

Animals↗
PubMed1984

Serum iron determination using ferene triazine.

The synthesis and characterisation of a new colorimetric reagent for iron, 3-(2-pyridyl)-5,6-bis(2-furyl)-1,2,4-triazine are described. Peak assignments and chemical shifts of the high resolution 13C nmr spectrum are given. The reagent forms a tris iron(II) complex with epsilon max of 32000 Lcm-1 mol-1 at 577 nm. The results of precision, linearity and recovery studies for use of the reagent in direct serum iron determinations are reported. Thiourea effectively suppresses copper interference for the serum iron determinations. With the procedure used, the presence of hemolysed cells in the serum had no effect on serum iron levels recorded.

Chromogenic Compounds↗
PubMed1984

Serum and CSF concentrations of testosterone and LH related to negative feedback in male rhesus monkeys.

Testosterone and LH concentrations were studied in blood and cerebrospinal fluid (CSF) in 8 adult male rhesus monkeys. All males were initially intact and 7 were subsequently castrated and implanted with an ascending series of testosterone capsules. In 4 of the males, serum testosterone levels were significantly higher at 21.00 h than at 09.00 h when the monkeys were intact. Following castration of these 4 males, 4-10 testosterone capsules produced serum concentrations similar to those previously found at 09.00 h; levels equivalent to those at 21.00 h were attained with 12-14 capsules. The proportion of unbound testosterone in serum represented 2% of total serum concentrations, but increased to 4% at high serum concentrations (12-14 capsules). In contrast, the proportion of unbound testosterone in CSF represented 100% of CSF levels. The levels of testosterone in CSF remained at values equal to 2-3% of total serum concentrations throughout the study. The levels of unbound serum testosterone and testosterone levels in the CSF were similar throughout the study in 3 of the 4 monkeys. In the fourth animal, supraphysiological serum testosterone levels occurred with 12 and 14 implants, and, at this time, the level of testosterone in CSF was less than the concentrations of unbound testosterone in serum. Following an intravenous bolus injection of testosterone, the steroid rapidly entered CSF when either 6 or 14 capsules were in place. Although the clearance of testosterone was similar within either compartment during both treatments, the half-life of testosterone in CSF was significantly shorter than in serum at high serum concentrations (14 capsules). Serum and CSF LH levels rose rapidly after castration, reaching maximal levels 8-12 days later with CSF LH levels consistently representing 2-3% of serum concentrations. Post-castration LH concentrations did not change until nocturnal testosterone levels were reached (12-14 capsules), when LH levels were suppressed in both serum and CSF. Subsequent reduction of serum testosterone levels (to 6 capsules) maintained the low LH concentrations. Seemingly, high testosterone concentrations in either serum or CSF, equivalent to nocturnal levels in intact males, were required to initiate LH suppression, but not to maintain it.

Animals↗
PubMed1984

Role of gonadal and adrenal steroids in the impairment of the male rat's sexual behaviour by hyperprolactinaemia.

The sexual behaviour of male rats, castrated and testosterone-implanted, declined following induction of hyperprolactinaemia by domperidone. Treatment with oestradiol benzoate did not reverse this effect, and may have accentuated it. Oestradiol also amplified domperidone-induced hyperprolactinaemia. Testosterone or dihydrotestosterone (DHT) apparently delayed, but did not prevent, the gradual deterioration in sexual behaviour (prolonged ejaculation latencies) induced by domperidone, but this effect was not confirmed statistically. Adrenalectomy, followed by cortisol replacement, failed to prevent the behavioural effects of hyperprolactinaemia. No consistent changes in serum progesterone or corticosterone could be found in hyperprolactinaemic rats in which the adrenals had not been removed. In vitro formation of DHT from precursor testosterone was reduced in the amygdalae of hyperprolactinaemic rats, but not in the hypothalamus or caudal spinal cord. Oestradiol cytosol binding was unchanged in all brain areas, except for a small but significant increase in the anterior hypothalamus. These results do not support a role for altered adrenal activity in determining the effects of high levels of prolactin on sexual behaviour. There is evidence for an impaired formation of DHT in the brain, but this may account for only part of the behavioural changes observed. It is possible that the major effect of prolactin lies in neural systems directly responsive to it, rather than in altered steroid secretion or metabolism.

Adrenal Glands↗
PubMed1983

Differential penetration of three anterior pituitary peptide hormones into the cerebrospinal fluid of rhesus monkeys.

This paper demonstrates marked differences between blood levels and those in the CSF for three anterior pituitary peptide hormones, prolactin, luteinizing hormone (LH) and adrenocorticotrophin (ACTH) in the rhesus monkey. CSF levels of endogenous prolactin (measured by radioimmunoassay) are about 20% of those in the blood, and this proportion remains constant under conditions of persistent ('steady-state') hyperprolactinaemia (induced by injecting sulpiride). Acutely elevating prulactin, by either an intravenous injection of exogenous ovine prolactin, or sulpiride, resulted in similar rates of entry by prolactin into the CSF, suggesting that retrograde portal flow is not an important mechanism. LH, measured by bioassay, is also present in the CSF, but the CSF/blood ratio is 5-10 times less than for prolactin. Castration, causing blood LH levels to rise, resulted in equivalent changes in CSF, so that the ratio remains constant, though still much lower than for prolactin. There are significant correlations between individual animals in the blood and CSF content of prolactin and LH. In marked contrast, whilst ACTH is found (by cytochemical assay) in the CSF of both intact and adrenalectomized monkeys, no significant change in CSF levels occurs despite 10-fold changes in the plasma of adrenalectomized animals following withdrawal of cortisol. Nor is there any correlation between blood and CSF ACTH levels over a wide range of concentrations. These results show that each of the three peptides studied has a distinct pattern of entry into the CSF from the vascular compartment.

Adrenalectomy↗
PubMed1983

The effects of intraventricular prolactin infusions on pituitary responsiveness to thyrotropin-releasing hormone, 5-hydroxytryptophan or morphine in rhesus monkeys.

The effects of intraventricular infusions of ovine prolactin (oPrl) on both endogenous prolactin levels in serum, and upon the release of prolactin and cortisol in response to treatment with either TRH, 5-HTP or morphine were studied in rhesus monkeys. A single injection of oPrl (10.8 micrograms) into the lateral ventricles of castrated males resulted in CSF levels of around 350 ng/ml 60 min later, but no oPrl could be detected in the blood. Endogenous (rhesus) prolactin levels in serum fell during this time to about half their initial values in oPrl-treated animals but not in the bovine serum albumin (BSA)-injected controls. Ovine prolactin was infused continuously into either the lateral or third ventricles of ovariectomized, estrogen-treated females for 6 days from an osmotic minipump (2.7 micrograms/h). CSF levels of oPrl were about 250 ng/ml though none was found in the serum. The release of endogenous prolactin by TRH (1 microgram) was greatly reduced compared with BSA-treated controls. 5-HTP (2.5 mg/kg together with carbidopa pretreatment) also stimulated much less prolactin release in females chronically infused with oPrl and there was some evidence for a similar effect in males following a single intraventricular injection. CSF levels of 5-HTP itself, and of 5-HIAA and HVA were similar throughout this experiment in both oPrl and BSA-infused animals. Finally, prolactin released by morphine (5 mg) was highly attenuated in females receiving oPrl intraventricularly. In contrast to those on serum prolactin, the effects of these various treatments on serum cortisol were unaltered by intraventricular oPrl. These results suggest that the primate brain contains a neural system which is directly responsive to prolactin, and which can modulate this hormone's release under either basal conditions or following treatment with substances that stimulate its release by acting either directly on the pituitary or upon the neural systems regulating pituitary function. These results are compatible with the presence of increased dopamine in the portal blood, though this was not measured in these experiments.

5-Hydroxytryptophan↗
PubMed1983

Unusual presentation of vitamin A intoxication.

A 10.5-year-old boy was admitted to hospital because of a focal motor seizure. He had suffered from impaired attention span and emotional instability from the age of 6 years. From the age of 5 years he received daily a multivitamin preparation containing 5,000 IU vitamin A. The cause of his symptoms was found to be vitamin A intoxication, with an unusual acute presentation of microscopic hematuria, electroencephalographic abnormalities, and convulsions.

Child↗
PubMed1983

Factors regulating levels of cortisol in cerebrospinal fluid of monkeys during acute and chronic hypercortisolemia.

Cortisol levels in the serum and cerebrospinal fluid (CSF) were studied in ovariectomized, estrogen-treated monkeys during either prolonged hypercortisolemia or the more transient effects of a bolus injection of cortisol. Control (saline-treated) animals showed the expected diurnal rhythm in serum cortisol, but proportionately more cortisol was present in the CSF when serum levels were high (i.e. in the morning). Prolonged hypercortisolemia for up to 37 days was produced by either thrice daily injections of cortisol itself or single daily injections of ACTH1-24 in the morning. Both treatments produced disproportionately larger amounts of cortisol in the CSF than in the serum, and the CSF/serum cortisol ratio was increased. Furthermore, prolonged ACTH treatment caused a marked elevation in CSF cortisol in afternoon samples taken at 16.30 h compared with those at 10.00 h, in the absence of a similar change in serum cortisol levels. The relative importance of entry and clearance of cortisol in the CSF in these conditions was studied in several ways. 'Free' cortisol levels in serum (determined by equilibrium dialysis) were equal to CSF cortisol levels in control monkeys, but were less than those in the CSF of hypercortisolemic animals. Entry of cortisol into CSF after a bolus injection was rapid, but, unlike serum, CSF cortisol levels did not decline significantly over a 70-min sampling period and the delayed clearance from the CSF could account for some of the effects seen during hypercortisolemia. Neither high levels of prolactin (which is elevated together with cortisol in 'stress'), induced by giving sulpiride, nor treatment with progesterone (which is also bound by corticosteroid binding globulin) altered the distribution of cortisol between blood and CSF. The concentrations of cortisol in the CSF therefore are regulated by factors influencing both its entry and clearance from the cerebral compartment. Neural tissues sensitive to cortisol are thus exposed to levels of this hormone that are both qualitatively and quantitatively different from those expected by direct extrapolation from serum levels.

Animals↗
PubMed1982

Relationship between prolactin in the serum and cerebrospinal fluid of ovariectomized female rhesus monkeys.

The entry of prolactin into the cerebrospinal fluid from the blood, and the relation between levels in the two compartments were studied under a variety of conditions in ovariectomized rhesus monkeys. Prolonged treatment with either domperidone or sulpiride, both dopamine-receptor blockers, elevated prolactin levels in serum and cerebrospinal fluid proportionally equally, so that the cerebrospinal fluid serum ratio was unchanged from controls (circa 12-20%). Gel filtration showed that only 'little' (monomeric) prolactin entered the cerebrospinal fluid in such monkeys. Following acute elevations of blood prolactin after a single injection of either sulpiride or ovine prolactin, cerebrospinal fluid levels increased linearly over a 90 min sampling period, despite falling serum levels. The rate of entry of prolactin into the cerebrospinal fluid was similar after either procedure, and was independent of absolute serum or cerebrospinal fluid levels, suggesting a rate-limiting mechanism. Furthermore, retrograde portal blood flow from the pituitary is not necessary to account for these results. Clearance of prolactin from the third ventricle was studied following intraventricular injection of prolactin. Prolactin was removed from the cerebrospinal fluid by a mechanism whose efficiency compares with that in serum, so that the half-life of prolactin in either compartment is about the same. Measurement of sodium, potassium and calcium in the cerebrospinal fluid during prolonged hyperprolactinaemia showed no change, indicating that the central effects of prolactin are not due to alteration of these electrolytes. These results show that cerebrospinal fluid levels of prolactin, and hence, those surrounding the brain, can be inferred accurately from those in the blood, and suggest that there may be a selective mechanism regulating the entry of prolactin into the cerebral compartment.

Animals↗
PubMed1982

Impaired copulatory behaviour of male rats with hyperprolactinaemia induced by domperidone or pituitary grafts.

Sexually experienced male CFHB rats, castrated and implanted with testosterone, were chronically treated with domperidone (ca. 5 mg/kg/day). Twice-weekly tests of sexual behaviour showed a significant elevation of both mount latency and ejaculation latency, and suppression of mounting rate after 2-3 weeks of treatment. The number of mounts and intromissions before ejaculation was increased on some tests by domperidone. Experienced male WAG rats, also castrated and testosterone implanted, received three pituitary grafts under the kidney capsule. An increase in ejaculation latency was seen during the first week and then again several weeks after grafting, though implantation of non-endocrine tissue (muscle) into the controls may also have affected behaviour. Both treatments elevated serum prolactin levels, domperidone much more substantially than pituitary grafts. Serum testosterone levels were sustained within the normal intact range by the implants. The weights of the seminal vesicles, ventral prostate and adrenal glands were not significantly altered by either treatment. These experiments show that hyperprolactinaemia induced by two independent methods can retard sexual behaviour in male rats.

Animals↗
PubMed1982

Drug-induced hyperprolactinaemia and discharges of luteinizing hormone evoked by oestrogen in ovariectomized rhesus monkeys.

Ovulatory failure associated with hyperprolactinaemia has been attributed to the inability of oestrogen to evoke a preovulatory discharge of gonadotrophins. This hypothesis was tested in ovariectomized rhesus monkeys rendered hyperprolactinaemic by treatment with two dopamine antagonists, domperidone, a compound reported not to cross the blood-brain barrier in rats, and sulpiride, a drug with known actions on both pituitary and central dopaminergic receptors. An artificial surge of oestrogen similar to that observed at mid-cycle in intact monkeys was obtained with subcutaneous capsules filled with oestradiol-17 beta. Treatment with either drug increased prolactin concentrations to 1.0 i.u./l or more compared with control values of 0.1-0.3 i.u./1. In the presence of these greatly increased prolactin levels, a normal discharge of LH, indistinguishable from that observed in control animals, was provoked by oestrogens in all but one drug-treated monkey. Furthermore, neither the basal (pre-oestrogen) level of LH nor the negative feedback action of oestrogen was consistently altered in hyperprolactinaemic monkeys. Administration of progesterone or 17 alpha-hydroxyprogesterone to simulate more closely the conditions observed in intact animals during the periovulatory period did not alter the LH discharge induced by oestrogen in animals treated with domperidone. The present results suggest that the high levels of prolactin brought about by dopaminergic blockade do not affect the positive feedback action of oestrogen. Furthermore, low levels of progestins do not sensitize the hypothalamic-pituitary axis towards an inhibitory action of prolactin on oestrogen-induced LH release. The rhesus monkey thus differs from other species, including man, in which artificially induced hyperprolactinaemia may impair or abolish the positive feedback action of oestrogen.

Animals↗
PubMed1981

Circadian rhythms in serum and CSF cortisol of rhesus monkeys, and their modulation by timed injections of L-5-hydroxytryptophan.

Levels of in serum and cerebrospinal fluid have been studied in male and female rhesus monkeys. Untreated animals showed circadian rhythms of cortisol in both compartments, highest values occurring at 08.00 h and lowest at 20.00 h, but the decline following the morning peak was slower in cerebrospinal fluid (CSF) than in serum. Both levels and CSF/serum ratios (c. 0.017-0.027) were similar in males and females. The ratio between highest and lowest points on the circadian rhythm was greater for CSF (males: 2.50; females: 2.63) than for serum (1.69 and 1.78). There were significant correlations between CSF and serum levels in individual monkeys at each of the four time points studied. No circadian rhythm in CSF homovanillic acid (HVA) or 5-hydroxyindoleacetic acid (5-HIAA) was found, nor any correlation between these monoamine metabolites and cortisol levels. Injecting cortisol once daily in the evening (18.00h) resulted in greater proportional elevation in the CSF than in serum cortisol in samples taken two hours later, and the values in the two compartments were no longer correlated at this time. There was no effect on CSF 5-HIAA levels, Injecting L-5-hydroxytryptophan (L-5-HTP) (2.5 mg/kg) at four different time points produced abnormal daily patterns of cortisol secretion, the peak following the injection of L-5-HTP. The distortion of the normal circadian rhythm thus induced was greater in the CSF than in he serum, and CSF/serum ratios were increased one hour following L-5-HTP administration. The data suggested, but did not prove, that L-5-HTP injection may have produced the least Proportional elevation of cortisol at 08.00 h (at the time of normal daily maxima). 5-HIAA, but not HVA, was elevated one hour after L-5-HTP to 2-3 ties normal . A dose of 0.2 mg dexamethasone at 23.00 h suppressed cortisol levels in serum examined at 08.00 h the next day. This suppression was partially reversed by giving L-5-HTP one hour before taking the next morning's sample. Rhythmic and episodic changes in serum cortisol thus have a proportionally greater effect on the daily pattern of cortisol level in the CSF (and hence the cerebral compartment) than that in the vascular compartment, and thus the exposure of cortisol-sensitive tissues in the two compartments to cortisol may differ.

5-Hydroxytryptophan↗