Biomedical subjects

N D Martensz

Publications and source records attributed to N D Martensz.

At least 19 recordsLinked to original sources

PubMed2001

Early growth restriction, membrane phospholipid fatty acid composition, and insulin sensitivity.

An animal model of protein restriction during pregnancy and lactation with subsequent dietary fatty acid manipulation was used to investigate the association between poor early growth, defective unsaturated fatty acid handling, and later disease. Both control and early growth-restricted animals fed a diet rich in saturated fatty acids showed a doubling of the plasma insulin levels as well as a reduced degree of unsaturation in liver and skeletal muscle membrane phospholipids compared with animals fed diets rich in unsaturated fatty acids. The skeletal muscle of early growth-restricted animals weaned onto a saturated fat diet had reduced proportions of 22:6n-3 and increased proportions of 18:1n-9. This reduction in 22:6n-3 is similar to that observed in Pima Indians, a population with a high prevalence of type 2 diabetes.

Animals↗

PubMed2000

A common apolipoprotein B signal peptide polymorphism modifies the relation between plasma non-esterified fatty acids and triglyceride concentration in men.

Insulin and non-esterified fatty acids (NEFA) are important regulators of triglyceride metabolism. The relations between these compounds and the effect of a common 3 amino acid deletion in the apolipoprotein B (ApoB) signal peptide (SP) following an oral glucose challenge have been investigated. The frequency of the shorter SP-24 allele was 32% (95% C.I. 29.5-36.5) in 725 subjects undergoing an oral glucose tolerance test (OGTT). Fasting plasma triglyceride concentration was positively correlated with fasting plasma insulin concentration and negatively with the degree of plasma NEFA suppression following the glucose challenge. Linear regression analysis showed the relation between triglyceride concentration and NEFA suppression, but not the relation between triglyceride concentration and fasting insulin, to be altered by the SP polymorphism in men but not in women. The strength of the association was dependent on the number of SP-24 alleles, with SP-24 homozygotes showing the greatest dependence (men P=0.031, women P=0. 914). It was proposed that the complex regulation of very low density lipoprotein (VLDL) output by NEFA and by insulin may explain, at least in part, the conflicting reports concerning the presence of the ApoB SP polymorphism, fasting serum lipids and ischaemic heart disease (IHD).

Adult↗

PubMed1998

Maternal low protein diet in rats programmes fatty acid desaturase activities in the offspring.

Numerous studies show an association between poor fetal growth and adult insulin resistance. Recent studies have shown relation between the long chain polyunsaturated fatty acid composition of skeletal muscle membranes and insulin sensitivity. More detailed analysis has indicated that the activity of delta5 desaturase is inversely correlated to insulin resistance. The amount of docosahexaenoic acid (C22:6n3) is also thought to play a part in determining insulin sensitivity. The purpose of this study was to test the hypothesis that early growth retardation in the rat, as a result of maternal protein restriction, would lead to alterations in desaturase activities similar to those observed in human insulin resistance. There were no differences in phospholipid fatty acid composition in liver or muscle from control and low protein rats. In both muscle and liver the ratio of docosahexaenoic acid to docosapentaenoic acid was, however, reduced in low protein offspring. Direct measurement of delta5 desaturase activity in hepatic microsomes showed a reduction (p < 0.03) in the low protein offspring which was negatively correlated (r = -0.855) with fasting plasma insulin. No correlation was observed in controls. These results show that it is possible to programme the activity of key enzymes involved in the desaturation of long chain polyunsaturated fatty acids. This is possibly a mechanism linking fetal growth retardation to insulin resistance.

Adult↗

PubMed1998

Increased PAI activity and PAI-1 antigen occurring with an oral fat load: associations with PAI-1 genotype and plasma active TGF-beta levels.

Whether the post-prandial lipemic response is linked to potentially pro-atherogenic and/or prothrombotic changes in plasminogen activator inhibitor (PAI) and transforming growth factor-beta (TGF-beta) is uncertain. The aim of our study was to determine whether PAI-1 antigen and PAI activity were elevated during post-prandial lipemia following a standard fat tolerance test. We also investigated changes in TGF-beta1 antigen and TGF-beta activity, to determine whether changes in TGF-beta activity were associated with changes in PAI measurements. Lastly, the influence of genotype at a common insertion/deletion polymorphism in the PAI-1 promoter on changes in PAI activity and PAI-1 antigen was examined. Fat tolerance tests were undertaken in 57 healthy middle-aged men to investigate associations between plasma concentrations of lipoproteins, PAI (antigen and activity) and TGF-beta. PAI-1 concentration increased by 76% after 8 h (P < 0.0001). PAI activity also increased by 64% (P = 0.0054) and TGF-beta activity decreased by 10% (P < 0.0001). Increases in PAI-I antigen and PAI activity varied markedly between individuals. To investigate these heterogeneous responses we examined whether genotype at the common insertion/deletion polymorphism of the PAI-1 promoter accounted for these differences. Individuals with at least one 4G (deletion) allele showed potentially pro-atherogenic changes in both PAI-1 and TGF-beta, compared to individuals who were homozygous for the 5G (insertion) allele. In conclusion, increased PAI and decreased TGF-beta activity occur during a fat tolerance test and this effect may be modulated by a common insertion/deletion polymorphism in the PAI-1 promoter.

Aged↗

PubMed1997

Is an exaggerated postprandial triglyceride response associated with the component features of the insulin resistance syndrome?

To investigate whether individual component features of the insulin resistance syndrome were associated with the postprandial triglyceride response, 57 healthy Caucasian men between 57 and 70 years of age underwent a fat tolerance test lasting 8 h. Fasting triglyceride concentrations were associated with the total unfractionated postprandial triglyceride response (r(s) = 0.54, p < 0.001) and the triglyceride-rich lipoprotein (TGRLP) fraction (d < 1.006) at 8 h was associated with the maximum non-esterified fatty acid concentration (NEFA) (r(s) = 0.33, p = 0.01). Measures of obesity (BMI and WHR) were not associated with the postprandial triglyceride response but were inversely related to NEFA suppression (NEFA nadir and BMI, r(s) = 0.31, p = 0.02; and NEFA nadir and WHR, r(s) = 0.36, p = 0.006). Other component features of the IRS, including glucose tolerance and two proxy measures of insulin resistance (fasting insulin concentration and HOMA measurement) were not associated with the postprandial triglyceride response despite being strongly associated with fasting triglyceride concentration. Current smoking habit, chronic alcohol consumption and birth weight were also not associated with an altered postprandial triglyceride response. In conclusion these results show that although component features of the IRS were associated with increased fasting triglyceride concentrations many of these features, including two proxy measures of insulin sensitivity were not associated with an exaggerated postprandial triglyceride response.

Aged↗

PubMed1996

The association between free fatty acid concentrations and triglyceride-rich lipoproteins in the post-prandial state is altered by a common deletion polymorphism of the apo B signal peptide.

To investigate whether there were associations between the free fatty acid (FFA) response during a fat tolerance test and changes in concentrations of triglyceride-rich lipoproteins 57 healthy Caucasian men between 57 and 70 years of age underwent a fat tolerance test lasting 8 h. FFA concentrations initially decreased from 0.75 +/- 0.03 to 0.64 +/- 0.03 mmol/l at 2 h and thereafter increased to 1.2 +/- 0.04 mmol/l at 8 h. Maximum FFA concentration was the only significant determinant of 8 h triglyceride-rich lipoprotein (TGRLP) concentrations (pooled chylomicron and VLDL fractions d < 1.006) (TGRLP-TG r = 0.33, P = 0.012; TGRLP apo B r = 0.37, P = 0.004; TGRLP cholesterol r = 0.38, P = 0.004). The strength of the association between FFA and TGRLP was affected by the apo B signal peptide genotype. Only in individuals who were homozygous for the 27 amino acid (SP27 or I) allele of the apo B signal peptide were there significant associations between maximum FFA concentration quartile and 8 h TGRLP concentration (P value for linear trend = 0.025). In this genotype group there were lower HDL cholesterol concentrations (1.16 mmol/l compared to 1.38 mmol/l in subjects either heterozygous or homozygous for the SP24 [D] allele; P = 0.005) and there was a trend toward increased 8 h TGRLP concentrations. We propose that the association between post-prandial FFA concentrations and post-prandial TGRLP concentrations in individuals who are homozygous for the SP27 allele may be linked to the increased prevalence of ischemic heart disease (IHD) in this genotypic group.

Aged↗

PubMed1989

Effects of expansion of blood volume and bilateral vagotomy on specific heart granules and release of atrial natriuretic peptide in the rat.

There was no statistically significant difference in basal concentrations of immunoreactive atrial natriuretic peptide (ANP), as assessed by radioimmunoassay, between right and left atrial muscle of control rats; similarly, stereological analysis showed no statistically significant difference in the fractional volume of myocytes occupied by specific heart granules, or in numerical density of granules, between right and left atria. Nevertheless, correlated radioimmunoassay and ultrastructural investigations showed that the major source of elevated plasma levels of ANP after expansion of blood volume was the right atrium. Substantial expansion of blood volume caused an increase in the proportion of peripherally located granules in myocytes of both atria, but reduction in the number of granules and in the concentration and total content of ANP occurred in the right atrium only. Bilateral cervical vagotomy also caused a statistically significant elevation of plasma ANP concentration, accompanied by a statistically significant reciprocal reduction in right atrial ANP content; no statistically significant change occurred in left atrial ANP. When blood volume was expanded after bilateral vagotomy, there was a further statistically significant increase in plasma ANP concentration; this was accompanied by further reduction in right atrial ANP and, moreover, the combined manoeuvre also elicited a statistically significant reduction of ANP in the left atrium. Ultrastructural studies confirmed that, under these conditions, myocytes in both atria showed a marked depletion of specific heart granules.

Animals↗

PubMed1989

Beta-endorphin concentrations in cerebrospinal fluid of monkeys are influenced by grooming relationships.

Social relationships are integral to the behaviour of many mammalian species. Primates are unusual in that their social relationships are extensive within groups, which often contain many reproductively active males and females. Several hypotheses have been forwarded to explain the ultimate causation of primate sociality. While attention has focused on grooming as a proximate factor influencing social relationships, the neural basis of such behaviour has not been investigated in monkeys. This report presents changes in the brain's opioid system contingent on grooming in monkeys. Opiates themselves have a feedback interaction with grooming behaviour, as revealed from the administration of opiate agonists and antagonists. Opiate receptor blockade increases the motivation to be groomed, while morphine administration decreases it. These data support the view that brain opioids play an important role in mediating social attachment and may provide the neural basis on which primate sociality has evolved.

Animals↗

PubMed1987

The effects of castration, testosterone replacement and photoperiod upon hypothalamic beta-endorphin levels in the male Syrian hamster.

Syrian hamsters kept in long day-lengths have active gonads and high circulating levels of gonadal steroids. Under the influence of the pineal gland, animals exposed to short photoperiods undergo testicular regression, have low circulating levels of testosterone and gonadotrophins and elevated levels of beta-endorphin within the hypothalamus. This paper describes the interaction between testosterone and photoperiod in the regulation of beta-endorphin levels in three regions of the hypothalamus. Hypothalamic beta-endorphin levels were measured by a combination of high-performance liquid chromatography and radioimmunoassay techniques that allows separation of the beta-endorphin (1-31) peptide from its metabolites and precursors. All of the beta-endorphin-like immunoreactivity in the hypothalamus of the male hamster, in both photoinhibited and photostimulated conditions, was found to represent the 31-amino-acid peptide. In photostimulated hamsters, chronic castration was associated with a significant increase of beta-endorphin levels in the anterior hypothalamus and mediobasal hypothalamus, which was reversed by treatment with exogenous testosterone. Castration prevented the ability of naloxone, an opiate receptor antagonist, to release luteinizing hormone, and this effect was also reversed by exogenous steroid. In photoinhibited hamsters, however, castration had no effect upon beta-endorphin levels in the preoptic area or mediobasal hypothalamus, and there was only a small increment in the anterior hypothalamus. Significantly, beta-endorphin levels in all areas of the hypothalamus of photoinhibited castrates were not decreased by testosterone treatment. In addition, administration of exogenous testosterone did not restore sensitivity to naloxone in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Relation between aggressive behaviour and circadian rhythms in cortisol and testosterone in social groups of talapoin monkeys.

Circadian rhythms in cortisol and testosterone in both blood and cerebrospinal fluid (CSF) were studied in four groups of male and female talapoin monkeys. Samples were taken 4 h apart under two conditions: whilst the sexes were kept separate (isosexual) and again after 24 h of interaction (heterosexual). There were similar rhythms in cortisol in males and females during the isosexual condition, though in blood (but not in CSF) mean levels were higher in females. Heterosexual interaction increased cortisol levels in both sexes (though more so in males), and also altered the shape of the rhythm, acrophase being delayed by 4 h in males and by 2 h in females. The amplitude of the rhythm was not altered. Cortisol levels were positively correlated in both males and females with the amount of aggression received from other males, but not from females nor with the animal's social rank. Circadian rhythms in serum testosterone in males were also altered by heterosexual interaction. Access to females delayed acrophase by 2 h, but had no effect on mean levels (unlike the effect on cortisol). As for cortisol, the amplitude of the testosterone rhythm remained unchanged. Serum testosterone was negatively correlated with aggression from males, but not from females nor with sexual interaction. This was associated with a pronounced decrease in the levels of testosterone during the night, not observed in males receiving no aggression from others. There was a non-significant trend towards a positive correlation between social rank and serum testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

PubMed1986

beta-Endorphin levels in the cerebrospinal fluid of male talapoin monkeys in social groups related to dominance status and the luteinizing hormone response to naloxone.

beta-Endorphin-like immunoreactivity was measured in the cerebrospinal fluid of 20 male talapoin monkeys living in mixed-sex social groups. It was shown that beta-endorphin was the major immunoreactive peptide; there was no evidence for high molecular weight precursors, or for either N-acetyl or C-shortened metabolites. Dominant males (those at the top of the social hierarchy) had lower levels of beta-endorphin than those of intermediate rank; subordinate males had higher levels than either of the other two ranks--about three times those measured in dominants. There were significant negative correlations between beta-endorphin in cerebrospinal fluid and both the amount of aggression given and sexual behaviour shown towards females. The response of the hypothalamo-pituitary system to opiate blockade was tested by giving the males naloxone in doses of 0.125, 0.25, 0.5, 1.0 and 5.0 mg/kg and assaying serum levels of luteinizing hormone 20 min later. Dominant males released significant amounts of luteinizing hormone at doses of 0.25 and higher; there was no release in either intermediate or subordinate monkeys at any dose. These findings show that an animal's rank in the social group in which it lives is strongly correlated with beta-endorphin levels in the cerebrospinal fluid, and with changes in the neuroendocrine response to opiate blockade. Altered opiate neural activity may be responsible for the depressed levels of sexual behaviour and gonadal function observed in monkeys at the bottom of the hierarchy.

Aggression↗

PubMed1985

Melatonin and the brain in photoperiodic mammals.

The reproductive cycle of photoperiodic species is driven by seasonal changes in daylength. The pineal gland transduces photic information into an endocrine signal. The duration of the nocturnal bout of melatonin secretion is a direct indicator of night-length. The circadian rhythm of melatonin production is driven by a multisynaptic pathway from the suprachiasmatic nuclei (SCN), via the parvocellular portion of the paraventricular nucleus to the preganglionic sympathetic neurons of the thoracic spinal cord. The melatonin signal acts as an interval timer. The cellular basis of the detection of the signal is unknown. The site of detection is possibly within the anterior hypothalamus. The SCN are not essential components of the system that responds to the pineal interval timer. Photoperiod and the pineal melatonin signal have pronounced effects on the function of endogenous opioids, which are probably related to changes in the neuroendocrine mechanisms that regulate gonadotropin release.

Animals↗

PubMed1985

Changes in the processing of beta-endorphin in the hypothalamus and pituitary gland of female rats during sexual maturation.

Puberty in the female rat is accompanied by a marked attenuation of the opioid inhibition of luteinizing hormone secretion. One factor which may contribute to this altered role is a change in the metabolism of opioid peptides during sexual maturation. beta-Endorphin undergoes a considerable degree of metabolism through both C-terminal proteolysis and N-acetylation, and these metabolites do not possess opioid activity. The processing of beta-endorphin in the hypothalamus and in the anterior and neurointermediate lobes of the pituitary gland in prepubertal and adult female rats was studied using gel filtration and high performance liquid chromatography coupled with radioimmunoassay. In the anterior lobe, high molecular weight precursors of beta-endorphin (pro-opiomelanocortin and beta-lipotropin) were present in prepubertal (28 days old) rats, but little authentic beta-endorphin was detected. In contrast, only beta-lipotropin and beta-endorphin were present in mature (70 days old) animals. Only beta-endorphin-sized peptides were present in the neurointermediate lobes of both prepubertal and adult rats. However, the proportion of N-acetylated metabolites was higher in sexually mature animals. In the hypothalamus, only beta-endorphin-sized peptides were present in both juvenile and adult animals. However, C-terminal proteolysis increased with age (no acetylated metabolites were detectable in this tissue). The proportion of the total beta-endorphin-like immunoreactivity attributable to beta-endorphin was lower in young adult (first dioestrus after vaginal opening) (55%) and mature (dioestrus, 61-64 days old) rats (56%) compared to prepubertal (30 days old) animals (75%) and the proportions of non-acetylated metabolites [beta-endorphin-(1-27) in young adults and beta-endorphin-(1-26) in adults] were increased concomitantly. These changes were correlated with a reduced luteinizing hormone response to the opiate antagonist naloxone in adult compared to prepubertal rats. beta-Endorphin is processed differently in the two lobes of the pituitary gland and in the hypothalamus and the degree of metabolism increases as the rat reaches sexual maturity. The increased metabolism of beta-endorphin in the hypothalamus, the site most likely to be involved in the control of luteinizing hormone secretion, results in a reduction in the relative proportion of the opioid active parent peptide. Thus, increased inactivation of beta-endorphin may contribute to the attenuation of the opioid inhibition of luteinizing hormone secretion observed during puberty.

Animals↗

PubMed1985

Annual reproductive rhythms in mammals: mechanisms of light synchronization.

Animals restrict the time of birth of offspring to the most advantageous time of year, usually spring or summer. This is achieved by controlling the preceding period of fertility and, in some cases, by delaying implantation of the zygote. Seasonal changes in daylength, the principal, though not the only cue, regulate pulsatile release of hypothalamic releasing factors that in turn activates the pituitary-gonadal axis. The role of the neuroendocrine system is therefore to translate the photoperiodic stimulus into an endocrine signal (Figure 12). The measurement of day length is a function of the circadian system, environmental light being sampled on a 24-hour basis. Experimental manipulations of the photoperiodic response have revealed the existence of a rhythm of sensitivity to the presence of light that is entrained by the prevailing photoperiod. Light falling within the period of maximal sensitivity results in an LD type response. It is important to note that although different species measure day length in a similar manner, the gonadal response to a given photoperiod will vary between species depending upon the nature of their seasonal reproductive strategy. Photic information is conveyed from the retina to the pineal gland by way of the suprachiasmatic nuclei of the hypothalamus and the cervical sympathetic trunk. The central connections between these structures are poorly understood. The pineal is an essential mediator of the photoperiodic response. The effects of pinealectomy vary between species, but in all cases the responses to changes in day length are blocked. The gland is neither anti- nor progonadotrophic; it merely provides a signal. This signal is probably the nocturnal release of melatonin. Studies on in vivo melatonin production and the responses of photoperiodic species to timed administration of exogenous melatonin have suggested that the duration of nocturnal melatonin production by the pineal is read by the CNS as an indicator of the length of darkness. This model for PTM provides a physiological basis to the observed rhythm of sensitivity to light. This period of sensitivity is probably a parallel to the nocturnal rhythm of melatonin production. Light falling in this phase blocks melatonin production, truncates the pineal signal, and hence produces an LD response by the CNS. The site of the signal detector is not known, although the anterior hypothalamus may be involved. How the pineal signal triggers changes in the hypothalamic LHRH pulse generator is not known. The endogenous opioids, however, especially beta-END may have a major role in exercising photoperiodic control over pituitary action.

Animals↗

PubMed1985

Changes in photoperiod alter the daily rhythms of pineal melatonin content and hypothalamic beta-endorphin content and the luteinizing hormone response to naloxone in the male Syrian hamster.

This study examines the possible involvement of beta-endorphin in the photoperiodic control of reproduction in the Syrian hamster. beta-Endorphin and LHRH concentrations in the medial basal hypothalamus (MBH), anterior hypothalamus (AHA), and the preoptic area (POA) as well as pineal melatonin content were determined by RIA in male Syrian hamsters exposed to either a long day [(LD) 16-h light; 8-h dark; lights on 0700-2300] or short day [(SD) 8-h light, 16-h dark; lights on 0700-1500] for 8 weeks. Groups of eight animals from each photoperiod were killed by decapitation at 4-h intervals over 24 h. Twenty minutes before death half the animals from each photoperiod were given naloxone (5 mg/kg, sc), the other half saline. Exposure to a long photoperiod maintained testicular activity while a short photoperiod induced testicular regression. Pineal melatonin content in both photoperiods was maximal at 0500 h, i.e. 2 h before the onset of light (SD, 435.58 +/- 82.7 pg/pineal; LD, 276.78 +/- 56.8 pg/pineal). However, the duration of the nighttime rise in pineal melatonin content was increased in SD animals with elevated melatonin levels at 2100 h (157.10 +/- 41.8 pg/pineal) and 0100 h (199.11 +/- 58.9 pg/pineal). In contrast pineal melatonin content in LD animals was only higher than daytime values at 0500 h. A daily rhythm of beta-endorphin content within both the AHA and MBH of animals exposed to a short photoperiod coincided with this prolonged nighttime rise in pineal melatonin content, although a causal relationship between the two was not established. Peak levels of beta-endorphin occurred at 2100 h (AHA, 6.569 +/- 1.2 pmol/mg protein; MBH, 4.877 +/- 0.45 pmol/mg protein) and at 0100 h (AHA, 6.107 +/- 0.66 pmol/mg protein; MBH, 4.49 +/- 00.79 pmol/mg protein) which was 6 h and 10 h into the dark phase, respectively, with lowest levels in the middle of the light phase (AHA, 3.561 +/- 0.56 pmol/mg protein; MBH, 2.688 +/- 0.3 pmol/mg protein). This rhythm was absent in animals exposed to a long photoperiod. There was no effect of photoperiod or time of day on the content of beta-endorphin in the POA. LHRH levels were not altered by changes in photoperiod in all three brain regions studied. In the AHA and MBH, concentrations of LHRH were similar at all times of day whereas, in the POA, LHRH levels varied with time in both photoperiods. Peak levels occurred in the middle of the dark phase at 0100 h (LD, 2.774 +/- 0.24 pmol LHRH/mg protein; SD, 3.206 +/- 0.48 pmol LHRH/mg protein) with lowest levels during the light phase (LD, 1.664 pmol LHRH/mg protein; SD, 1.775 pmol LHRH/mg protein).(ABSTRACT TRUNCATED AT 400 WORDS)

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↗

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↗