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Biomedical subjects

W Wuttke

Publications and source records attributed to W Wuttke.

At least 217 records · Page 12Linked to original sources

Development of stress-induced pituitary prolactin and TSH release in male rats.

Blood was collected from male rats of various ages under control conditions and after introduction of two stress factors. All animals were sacrificed between 15.00 and 16.00 h. Serum prolactin levels in immature male rats were found to be very low between birth and day 15 after birth. Neither exposure to a new environment, for example removal from the animal rooms for the duration of 10 min, nor exposure to concentrated ether vapour resulted in increased serum prolactin levels. Between day 20 and 35 basal serum prolactin levels were increased, they then fell at adult values. During this period of increasing serum prolactin levels pituitary prolactin release became stress-susceptable; i.e. elevated serum prolactin levels were observed after introduction of stress factors as in adult male rats. Serum TSH levels were found to be high between birth and day 10. Low TSH levels measured between day 15 and 40 and adult values were detected after day 40. Neither ether nor removal of the animals from their normal environment changed serum TSH levels at any age tested. The results indicate that the hypothalamo-pituitary in immature rats reacts in a similar way as that in adult animals from day 16-20 onwards. Serum TSH levels in these animals, however, are reduced, indicating that an increase in serum TSH is not necessary for normal processes of maturation.

Age Factors↗

HCG-binding capacity of the rat ovary during pregnancy.

During pregnancy, binding of 125I-labelled HCG to the rat ovary increases markedly from the 3rd to the 17th day of pregnancy but is reduced drastically at the end of pregnancy and after delivery. At the 17th day of pregnancy the HCG-binding capacity of the rat ovary is raised 76-fold in comparison to oestrous rats (17th day of pregnancy: 128 X 10(-15) mol/mg wet weight; oestrus: 1.67 X 10(-15) mol/mg wet weight). It is assumed that only LH receptors not occupied by endogenous hormone are covered by our assay. The high number of "free" ovarian HCG receptors during pregnancy apparently represents "Spare" receptors, the functional significance of which remains unclear. It is suggested that the metabolic activity of the ovarian luteal cells during pregnancy is not restricted by the number of HCG receptors present, but through the level of the endogenous gonadotrophic hormone and/or some unknown factors residing in the luteal cell.

Animals↗

Desensitization of the dopaminergic inhibition of pituitary luteinizing hormone release by prolactin in ovariectomized rats.

Increase of plasma prolactin in chronically ovariectomized rats by transplanting pituitary glands from male rats to the kidney capsule reduced pituitary LH output for 1 week. At the end of this time, despite the fact that prolactin remained high, plasma LH levels rose to reach the value seen in ovariectomized control rats. High plasma prolactin did not affect FSH concentrations. Treatment of ovariectomized rats with apomorphine, a dopamine-receptor stimulating drug, reduced pituitary LH release in a dose-dependent way at doses of 1, 2, 5 and 10 mg/kg body weight. Higher doses either had no effect or they stimulated pituitary LH release. Apomorphine did not reduce pituitary LH secretion in chronically hyperprolactinaemic rats at doses which significantly inhibited LH release in ovariectomized animals. Plasma FSH levels were not affected by apomorphine treatment. In both groups of animals the drug reduced plasma prolactin levels to basal values, indicating that the dopamine agonist inhibits pituitary prolactin release by direct action on the pituitary gland. These results suggest that dopamine inhibits pituitary LH release, probably by reducing hypothalamic LH-releasing hormone release. The mechanism by which chronically high prolactin levels cause apomorphine to be less effective in reducing pituitary LH release may be a desensitization of some dopamine-receptive mechanism which is inhibitory to LH release.

Animals↗

Effects of intraventricular 6-hydroxydopamine injections on serum prolactin and LH levels: absence of stress-induced pituitary prolactin release.

The drug 6-hydroxydopamine (6-OHDA) has been reported to reduce hypothalamic norepinephrine (NE) content after administration into the lateral ventricle without altering the dopamine content of tubero-infundibular neurons. Serum prolactin levels in male rats injected with 2 X 250 mug 6-OHDA were significantly higher than in untreated control rats. Intraventricular injection of male rats with artificial cerebrospinal fluid resulted in elevated mean prolactin levels similar to those observed in 6-OHDA-treated animals. Further experimentation on animals decapitated at different times after removal from the animal quarters, indicates that prolcatin levels in 6-OHDA-treated rats are continuously elevated whereas they rise from basal levels to extremely high levels in CSF-treated rats, thus resulting in similar mean values. The CSF-treated controls ate hypersensitive to the stress of being removed from their normal environment. Such an effect was not observed in 6-OHDA-treated nor in untreated, and thus stress-inexperienced rats. In a long term study, serum prolactin and luteinizing hormone (LH) levels were followed over a period of 71 days after 6-OHDA treatment. Prolactin levels increased within one day after treatment and stayed at a high level for 15 days. Subnormal prolactin values were measured 37 days after 6-OHDA treatment. Serum LH levels were below normal 3 h and one day and were increased 37 and 71 days after 6-OHDA treatment. These results suggest that NE is important in the transmission of stressful stimuli to hypothalamic prolactin regulating centers. They further suggest functional recovery of LH and prolactin regulating mechanisms after 6-OHDA treatment.

Animals↗

EEG changes during spontaneous and controlled menstrual cycles and their correlation with psychological performance.

1. EEG (occipito-central, anterior and posterior temporo-central), blood concentration of hormones (oestradiol, progesterone, prolactin, folliculo-stimulating (FSH) and luteinizing (LH) hormones) and psychometric tests (reaction time, concentration, simple calculations, visual orientation and simple motor performance tasks) were recorded from 16 young women during a spontaneous menstrual cycle (s.c.w. group) and from 16 women taking combined oral contraceptives (o.c.w. group). All data were collected every second day except Sundays. 2. The EEGs underwent power spectrum analysis. Power and weighted mean frequency were determined for different frequency bands (theta, alpha and beta). The most constant finding in the s.c.w. group was a slight increase of mean alpha frequency during the luteal phase until menstruation (mean of occipital alpha acceleration = +0.3c/sec). The average time course of this acceleration fitted the time course of progesterone increase, but no direct correlation could be established. No such acceleration of alpha frequency could be found in the o.c.w. group, but the mean frequency in this group was about 0.5c/secslower than that of the s.c.w. group. In addition, minor cyclic changes of EEG paramenters in the s.c.w. group were observed in the occipital and temporal theta activity, the temporal alpha activity, but none in the beta range. 3. Reaction times to simple tasks, simple arithmetic, etc. were slightly but significantly decreased in the s.c.w. group during the luteal phase with a minimum on the day before or during menstruation. No such changes were observed in the o.c.w. group, which performed, in all tasks, slightly slower and slightly less correctly than the s.c.w. group. 4. The individual relative accelerations of alpha frequency and shortening of reaction times were positively correlated with each other.

Adult↗

Hyperprolactinemic anovulatory syndrome.

The functional status of the hypothalamo-pituitary-gonadal axis was investigated in 127 women with anovulatory disease. Radioimmunoassayable circulating LH, FSH, and prolactin concentrations were measured. An attempt was made to localize the functional lesion by utilizing the following criteria: 1. Hypothalamic function: a) clomiphene test based upon hormonal parameters; b) recording of the pulsatile LH fluctuation (spiking) and of basal FSH. 2. Pituitary function: determination of the gonadotropin reserve by means of a standardized LRH test. 3. Ovarian function: a) measurement of plasma E2 and progesterone levels by RIA; b) gestagen bleeding test. All patients had amenorrhea of up to 14 years duration. A total of 17 hyperprolactinemic patients (13.4%) was found. Eight of these patients never experienced galatorrhea, in 7 only transient galactorrhea was reported, and in 2 cases galactorrhea persisted. All hyperprolactinemic patients were found to be clomiphene non-responders as well as nonspikers. The pituitary LH reserve varied from practically none to normal. Baseline LH was low whereas that of FSH was normal. In accordance with this observation E2 levels, with two exceptions, were found to be in the lower range of normal female concentrations. Thus, all but two patients exhibited gestagen withdrawal bleeding. In conclusion, the hyperprolactinemic anvoluatory syndrome is not necessarily associated with galactorrhea. In all cases of amenorrhea syndromes with or without galactorrhea, hyperprolactinemia should be excluded as it is very often associated with anovulation. The hyperprolactinemic anovulatory syndrome includes the following features: 1. gestagen withdrawal bleeding. 2. subnormal to normal E2 levels. 3. clomiphene nonresponsiveness. 4. LH-hypogonadotropism. 5. lack of LH secretory episodes. 6. FSH-normogonadotropism.

Adult↗

Circadian fluctuations of serum hormone levels in prepubertal male and female rats.

Diurnal variations in serum hormone levels during 2 different stages of prepubertal development were investigated in male and female rats. Groups of 13 to 18 and 25 to 30 day old male and female rats were decapitated at 4-hour by intervals during a period of 24 h. Their blood was collected and hormones were measured by radio-immunoassay. FSH levels were constantly high in 13 to 18, but low in 25 to 30 day old females. FSH was low in younger males, and significantly higher but without diurnal fluctuations in the older males. Serum LH was low in approximately 40% of the 13 to 18 day old females, while 40% had moderately high levels, and the remaining females extremely high levels of the hormone. Most of the extremely high LH peaks were found at 15.00 h and some at 03.00 h. Older females and males of both age groups had constantly low serum LH levels. Serum oestradiol was high in males and females during days 13 to 18, but it was lower in the 25 to 30 day old animals. In the young females prolactin was slightly elevated between 15.00 h and 19.00 h, while in the males the serum prolactin fluctuations were not significant. Serum testosterone was low in females at all times. The 13 to 18 day old males had higher testosterone levels than the 25 to 30 day old males. Both groups showed slight, but insignificant fluctuations in serum testosterone.

Age Factors↗

Oestrogens and prolactin as possible regulators of puberty.

At day 15 after birth, high serum oestradiol levels, high FSH levels and occasionally high LH levels were observed in control female rats. Injections of potent and specific antisera for oestrogen between days 8-15 prevented LH peaks and decreased basal LH levels. Serum FSH levels were increased after treatment. High oestradiol levels at this time appear to exert a positive feedback action on phasic as well as tonic LH release. Injections of ovine prolactin (0.5 mug/g body wt twice daily) between days 8-25 of life significantly advanced the day of vaginal opening in immature rats and initiated regular oestrous cycles. Such treatment completely prevented high LH levels at day 15 but serum FSH levels remained high. Prolactin and progesterone levels were higher at day 25 than at day 15 in control rats and at that time LH and FSH levels were low. Prolactin treatment had a depressant effect on endogenous prolactin and progesterone levels. It is proposed that after day 20 the positive feedback threshold of oestradiol on LH release is at a mature, highly sensitive level. The steady increment in serum prolactin and/or progesterone levels between day 20 and puberty, however, inhibited phasic LH release thus preventing early puberty. The possible mechanisms of action of prolactin are discussed.

Animals↗

Response of medial preoptic neurons to electrical stimulation of the mediobasal hypothalamus, amygdala and mesencephalon in normal, serotonin or catecholamine deprived female rats.

Single cell activity from preoptic neurons was extracellularly recorded in normal female rats and the effects of electrical stimulation of the mediocortical amygdala (AMY), the N. med. raphes (MES) and the mediobasal hypothalamus (MBH) was tested. 1. One type of preoptic neurons (55%) reacted with primary excitation to a single electrical stimulus of AMY, MES or MBH, which was usually followed by a period of postexcitatory inhibition. Another type of neurons (29%) were first inhibited after stimulation of AMY, MES or MBH and then showed a period of postinhibitory excitation. The discharge rate of a third type was not affected by electrical stimulation of these structures (16%). If a neuron was affected by a stimulus in a given area it predictably reacted in the same fashion to stimulation of the other areas. 2. The postexcitatory inhibition of the majority of the primarily excited neurons was strong enough to prevent the stimulus response to a second stimulus. Occasional recordings from two neighboured cells simultaneously indicate that they can be inhibitory to each other. 3. By pulse train stimulation of the AMY or MES with varying frequencies it could be demonstrated that low frequencies (10 Hz) had a facilitatory action whereas higher frequencies (100 Hz) were inhibitory to preoptic discharge rates. 4. No obvious alteration of neuronal properties we found neither in rats treated intraventricularly with 5,6-dihydroxytryptamine, which strongly reduces central nervous system serotonin content, nor in 6-hydroxydopamine treated rats, which had low central nervous system catecholamine levels.

5,6-Dihydroxytryptamine↗

Changes with age in levels of serum gonadotropins, prolactin and gonadal steroids in prepubertal male and female rats.

Radioimmunological determination of serum LH, FSH, and estradiol concentrations in prepubertal female rats demonstrates the temporal coincidence of increased serum levels of these hormones between days 9 and 21. Serum FSH and estradiol levels are continuously high during that time, whereas interindividual fluctuations in LH levels were enormous. No high LH, FSH, and estradiol levels were observed between day 21 and puberty, during which time serum prolactin and progesterone gradually increased. Serum testosterone in the female immature rats stayed uniformly low. It is suggested that increased serum estradiol levels in the presence of low prolactin levels (between day 10 and 20) act in a positive feedback fashion on the CNS-pituitary axis. The resulting increased gonadotropin levels are later (between day 20 and puberty) decreased by an inhibitory action of prolactin and/or progesterone on pituitary gonadotropin release. In male rats serum FSH and prolactin, which were low during the first 3 weeks, increased later to reach high levels during puberty. Serum LH was slightly elevated during the 2nd and 3rd week of life at which time serum progesterone also increased to reach the highest levels in the prepubertal period. Serum testosterone was higher in male than in female rats for the first 3 weeks of life; the difference between both sexes was significant but not striking. Between day 21 and the prepubertal period the testosterone levels were relatively low, but they increased again during puberty. Sex differences in androgen levels (measured with a less specific antibody) were more pronounced whereas estradiol levels in males showed the same pattern between birth and puberty as in the female littermates. These results suggest that not only testosterone but also other, not yet identified, androgens may be involved in the masculinzation of the brain.

Age Factors↗

Further studies on self-administration of antipyretic analgesics and combination of antipyretic analgesics with codeine in rhesus monkeys.

The possible reinforcing effect of acetylsalicylic acid (ASA) was studied in a group of rhesus monkeys that had no history of self-administration of drugs. Rates of lever pressing were compared under conditions in which each lever-pressing response resulted in an infusion of saline, an infusion of saline plus delivery of a food pellet or an infusion of ASA (0.4, 1.0, 2.5 OR 5.0 MG/KG /infusion). Responding was engendered and maintained by the delivery of food pellets but not by infusions of saline alone nor by ASA; however, responding was subsequently engendered and maintained in these monkeys by codeine (0.05 mg/kg/infusion). In another group of monkeys that had been trained to respond under a 10-response fixed-ratio schedule of i.v. infusions of codeine, the possible reinforcing effects of aminophenazone, phenylbutazone and of combinations of each of these drugs with codeine were studied. Aminophenazone and phenylbutazone (0.4-5.0 mg/kg/infusion) did not maintain responding previously engendered by codeine. Mixtures of aminophenazone and phenylbutazone with codeine decreased the number of codeine self-administrations. Thus, codeine intake was reduced when aminophenazone and phenylbutazone were added to codeine in the solution to be self-administered. These experiments suggest that antipyretic analgesics are not effective in reinforcing behavior in the rhesus monkey.

Aminopyrine↗