Serum luteinizing hormone follicle-stimulating hormone and prolactin in neonatal-androgenized rats.

Serum levels of LH, FSH, Prolactin and Testosterone of 90 days old male rats androgenized soon after birth were determined by specific radioimmunoassay and were compared to untreated rats. LH and FSH levels were also determined in 90 days old female rats neo-natally treated with testosterone and compared with normal diestrus rats. Androgenization of male rats significantly increased serum FSH and Prolactin levels without producing changes in plasma LH and testosterone concentrations. Similar increase in the FSH levels were found in androgenized female rats although plasma FSH concentrations were lower than in the male groups. These results obtained in male rats give an additional evidence that androgens acting in the first days of life are responsible of the higher levels of FSH and Prolactin that characterize the male or tonic pattern of gonadotrophin secretion.     

Therapy with bromocriptine and behavior of various hormones in psoriasis patients

The activity of bromocriptin has been clinically tested on 18 patients suffering from psoriasis. The plasma levels of Human Growth Hormone (HGH), Human Adrenocorticotropic Hormone (ACTH), Thyroid Stimulating Hormone (TSH), Prolactin (PL), Aldosterone and Cortisol were investigated in these 18 patients along with 35 untreated psoriatic patients and 19 normal subjects. Bromocriptin was shown to be effective in 13 of our 18 psoriatic patients. Plasma levels of HGH, ACTH, and Aldosterone, measured in all 53 psoriatic patients, were found to be higher than normal in 11, 26 and 40 patients respectively (HGH and Aldosterone: p less than 0,005; ACTH: p less than 0,001).     

A Substrate for Direct Measurement of L-iduronic Acid 2-sulfate sulfatase

Commercially available sodium heparinate has been sequentially treated with methanolic 0.06M hydrogen chloride and nitrous acid. The nondegraded material was separated by gel filtration from the nonsulfated and monosulfated disaccharides produced. The latter ones, obtained in 10% yield, have been used as a substrate for the direct measurement of the enzyme L-iduronic acid 2-sulfate sulfatase present in human plasma and fibroblast homogenates. Studies of the kinetics and pH optimum of the enzyme, by use of plasma of a patient with mucolipidosis II, indicated an apparent K_m of 2.5mM and a pH optimum of 4.6-4.8. The levels of activity in normal plasma and plasma of a patient with Hunter's disease were found to be 20.4 ± 1.22 units (μmol sulfate/24 h/g protein) and 3.25 ± 0.35 units, respectively. In homogenates of cultured skin fibroblasts, the levels were 137.6 ± 10.7 units for normal controls and 6.4 ± 5.1 for patients with Hunter's disease. The plasma of two obligated heterozygotes gave intermediate levels of activity, whereas the plasma of two possible heterozygotes gave either intermediate levels or entirely normal levels of activity.     

Prolactin levels in pregnancy: comparison of normal subjects with patients having micro- or macroadenomas after early bromocriptine withdrawal

14 previously infertile patients, 11 with radiologically abnormal fossae, and a mean prolactin level of 761 ng/ml (range 49-4,500 ng/ml) conceived on 19 occasions during bromocriptine treatment. So far, 15 healthy infants have been delivered. Treatment was withdrawn soon after conception and the subsequent prolactin changes compared with those of 44 normal subjects. Prolactin levels returned to pretreatment values in 7, but stayed within our normal range (less than 350 ng/ml) in the 6 remaining patients studied. No patient developed signs or symptoms of tumor enlargement. 2 patients, 1 of them with the largest tumor, have now normal prolactin levels and can be considered as cured. Bromocriptine treatment can restore fertility and be safely withdrawn during pregnancy even in patients presenting with large tumors. Nevertheless, patients should be carefully monitored and treatment with bromocriptine re-introduced if necessary.     

Prolactin secretion in a brood parasite, the brown-headed cowbird, Molothrus ater

Blood samples were collected from a free-living population of male and female brown-headed cowbirds, Molothrus ater , during the breeding season and plasma levels of prolactin were measured by radioimmunoassay. Prolactin concentrations in both sexes increased significantly in mid to late May; peak levels were reached by June and were maintained throughout June and into July. Prolactin levels in juveniles were significantly lower than in adults but were still elevated. Prolactin has been implicated in parental care in several avian species; however, cowbirds are brood parasites with complete absence of parental behaviour, suggesting that prolactin must function in another capacity in cowbirds, or that cowbirds have developed target tissue insensitivity to this hormone.     

Plasma Prolactin Activity in Inappropriate Lactation

Using a bioassay dependent on the development of a lactogenic response in rabbit mammary tissue cultured in vitro, prolactin distinct from immunoreactive growth hormone has been found in the plasma of patients of both sexes with inappropriate lactation with and without evidence of pituitary tumours. It has also been found in one patient with primary hypothyroidism and galactorrhoea, and in another during chlorpromazine therapy, but not in nine patients with gynaecomastia without galactorrhoea. Plasma prolactin levels were examined in seven patients during oral glucose tolerance tests: no change occurred in the four patients with pituitary tumours, but the levels were suppressed in the three patients with normal pituitary fossae. Prolactin appears to be a distinct pituitary hormone in man, as in animals, and also to be aetiologically related to states of inappropriate lactation.     

X-ray diffraction evidence for myelin disorder in brain from humans with alzheimer's disease

Wide-angle X-ray diffraction studies revealed that the lipid phase transition temperature of myelin from brain tissue of humans with Alzheimer's disease was about 12°C lower than that of normal age-matched controls, indicating differences in the physical organization of the myelin lipid bilayer. Elevated levels of malondialdehyde and conjugated diene were found in brain tissue from humans with Alzheimer's disease, indicating an increased amount of lipid peroxidation over the controls. An increase in myelin disorder and in lipid peroxidation can both be correlated with aging in human brain, but the changes in myelin from humans with Alzheimer's disease are more pronounced than in normal aging. These changes might represent severe or accelerated aging.     

Growth hormone and prolactin secretion in Huntington's disease.

Growth hormone (GH) and prolactin (PRL) secretion was studied in twelve patients with Huntington's Disease, eight unaffected relatives, and twenty normal subjects in response to provocative and suppressive tests. Prolactin responses to TRH, chlorpromazine, L-DOPA, and apormorphine were similar in all groups with the exception of a slightly blunted PRL response to THR in the unaffected relatives. Although GH responses to L-DOPA were similar in all groups, patients with Hungtinton's Disease had nearly absent GH responses to apomorphine (mean peak GH = 1.4±0.4 (SE) ng/m1) compared to normal control subjects (mean peak GH = 28.9±8.6 ng/m1). These results, which are similar to some previously reported findings in drug-induced tardive dyskinesia, suggest an abnormality in dopamine-mediated GH secretion in Huntington's Disease.     

Prolactin response to sulpiride in non insulin dependent diabetes mellitus

Blood glucose, insulin and prolactin concentrations were determined before and after sulpiride injection (50 mg i.m.) in 20 non-insulin-dependent diabetic patients (10 with retinopathy and 10 without evidence of retinal damage) and 10 subjects with normal glucose tolerance. Prolactin response to sulpiride was significantly higher in diabetics than in controls (at 20 min., p less than 0.01; at 30 and 60 min., p less than 0.005; at 90 min., p less than 0.01; at 120 min., p less than 0.05). The sulpiride induced hyperprolactinemia did not influence blood glucose and plasma insulin levels in controls as well as in diabetic patients. Prolactin response to sulpiride was the same in diabetics with and in those without retinal changes. We conclude that acute hyperprolactinemia seems to have no influence on glucose homeostasis in normal and non insulin-dependent diabetic subjects.     

Prolactin's mediative role in male parenting in parentally experienced marmosets (Callithrix jacchus)

Prolactin has been implicated in promoting paternal care behaviors but little evidence of causality has been found to date except for birds and fish. This study was designed to examine the possible causal relationships between prolactin and male parenting behaviors, reproductive hormones, and physical changes in cooperatively breeding common marmosets, Callithrix jacchus. Fifteen parentally experienced fathers were studied over three consecutive infant care periods during two weeks prior and three weeks following their mates' parturition under three-treatment conditions: normal control pregnancy, decreased prolactin and elevated prolactin. The treatments significantly altered the serum prolactin levels in the fathers. Using three methods of determining a father's level of parental care: infant carrying, family effort and responsiveness to infant stimulus tests, we found that only the male response to infant stimuli was altered by the hormone treatments. Lowering prolactin significantly reduced male responsiveness to infant stimuli but elevating prolactin showed the same effect. Hormonal sampling indicated that testosterone levels showed an inverse relationship to prolactin levels during a normal peripartum period and prolactin treatment reduced this relationship. Prepartum estradiol levels were significantly elevated during the lowered prolactin treatment and estradiol was significantly lowered postpartum with the elevated prolactin treatment. Father's weight decreased significantly by the third week of infant care during the normal treatment. Males in the elevated prolactin treatment lost little or no weight from prepartum while in the lowered prolactin treatment showed the most weight loss. The present findings did not distinguish a direct causal relationship of prolactin on behavior in experienced fathers but did find an interaction with other hormones and weight gain.     

精神分裂症患者中的高泌乳素血症研究进展

高泌乳素血症在精神分裂症患者中发生率高,主要原因为抗精神病药物和精神分裂症本身的作用。精神分裂症患者服用抗精神病药物后泌乳素水平较快升高,长期服用后泌乳素水平可能趋向于稳定甚至降低,但仍高于正常值。高泌乳素血症会导致肥胖等诸多不良后果。而精神分裂症患者服用抗精神病药物后另一常见的副反应是代谢相关不良反应,越来越多的研究开始关注兼顾治疗高泌乳素血症及肥胖、糖脂代谢异常的方法。溴隐亭、阿立哌唑及芍药甘草汤等中药具有一定的降低泌乳素水平的作用,但使用有限制性,且不能改善抗精神病药物所致代谢相关的不良反应。二甲双胍除了能改善糖脂代谢紊乱,还具有潜在的降泌乳素作用,对于同时有代谢异常如肥胖、糖脂代谢异常及高泌乳素血症的患者来说可能具有双重治疗效果,但其降泌乳素的疗效和剂量需要进一步的大样本临床研究。     

Effect of ACTH and prolactin on dehydroepiandrosterone, its sulfate ester and cortisol production by normal and tumorous human adrenocortical cells

The effect of ACTH and prolactin on the synthesis of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) was studied in cell suspensions of "normal" and tumorous (adenoma) human adrenal cortex. A stimulation of DHEA and no response of DHEAS production by ACTH in "normal" adrenocortical cell suspension was observed. However ACTH stimulated both DHEA and DHEAS synthesis in tumorous adrenocortical cells. Prolactin did not influence either the basal or the ACTH stimulated DHEA and DHEAS production of adrenocortical cells irrespective of their origin. Our results are compatible with the concept that the biosynthesis of DHEA is under ACTH control, while other factor(s) regulate(s) the sulfate pathway of DHEA secretion under normal conditions. In tumorous adrenocortical cells DHEA may be regulated--at least partly--by ACTH. Prolactin seems to have no direct effect on DHEA and DHEAS synthesis. It is postulated that the relationship between serum prolactin and DHEAS (or DHEA) levels observed by several authors might be an extraadrenal effect of prolactin on adrenal androgens.     

Long-term Treatment of Galactorrhoea and Hypogonadism with Bromocriptine

Seventeen women and four men with galactorrhoea and associated hypogonadism have been treated with bromocriptine for 2 to 28 months. In 18 patients the gonadal status became normal as the galactorrhoea improved. The gonadally unresponsive patients had either pituitary tumours or premature menopause. Prolactin levels fell with treatment; withdrawal of the drug was associated with an increase in serum prolactin and a recurrence of the galactorrhoea and hypogonadism. Two patients tried to become pregnant on treatment and both succeeded. Raised prolactin levels appear to block the actions of the gonadotrophins at a gonadal level rather than prevent their synthesis or release; lowering prolactin secretion with bromocriptine allows resumption of normal gonadal function. Bromocriptine appears to be the treatment of choice for inappropriate lactation in association with hypogonadism on a long-term basis.     

Regulation of seasonal reproductive activity in the stallion, ram and hamster

This review considers seasonal reproduction in male animals with emphasis on the stallion, ram and hamster. The pineal hormone melatonin is the common link between photoperiod and reproduction. An increase in the daily diurnal period of melatonin secretion is associated with a decrease in GnRH release in long-day breeders, but an increase in GnRH release in short-day breeders. Melatonin influences GnRH release within or close to the mediobasal hypothalamus in rams; whereas melatonin receptors have not been found in the hypothalamus of horses. Prolactin release is positively correlated with daylength. Prolactin concentrations are consequently low during the breeding season of sheep and high during the breeding season of horses and hamsters. Prolactin stimulates testicular function in rams. Seasonal changes in GnRH release in the horse are regulated by changes in a GnRH-inhibitory opioidergic tone. Opioids are at least, in part, responsible for the decrease in testicular function during winter. An opioidergic inhibition of LH release is present during the breeding season in rams; but dopaminergic pathways inhibit LH release during long daylight hours. A dopaminergic inhibition of LH release does not exist in stallions.     

Role of steroid hormones and prolactin in canine mammary cancer

In several animal studies, prolactin has been found to be essential for mammary epithelial development, and its administration has been consistently shown to increase the rate of mammary tumours. High levels of steroid hormones have also been suggested to enhance mammary cancer development. The present study investigates the levels of the following hormones in serum and in tissue homogenates in dogs bearing canine mammary tumours: prolactin (PRL), progesterone (P4), dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T), 17beta-estradiol (17beta-E2) and estrone sulfate (S04E1). Eighty mammary tumours (40 dysplasias and benign and 40 malignant tumours) from 32 female dogs, and 10 normal mammary glands from eight female dogs without history of mammary tumours, were analysed. Prolactin and steroid hormones in serum and tissue homogenates, were analysed by enzyme immunoassays (EIA) techniques, previously validated for this animal species. Levels of prolactin in tissue homogenates were significantly different between malignant and benign mammary tumours (p<0.01). Serum prolactin concentrations were lower in the control group as compared with the group of dogs with benign tumours and in dogs with malignant tumours (p=0.01). Serum prolactin levels in dogs with benign lesions were not significantly different than those obtained from dogs with malignant tumours. Levels of steroid hormones were significantly higher in malignant tumours compared with the benign tumours and normal mammary glands (p<0.01) both in serum and homogenate determinations. Our results suggest that the canine neoplastic mammary gland could be a source of prolactin. Our hypothesis is that both prolactin and steroid hormones are involved in the growth of canine mammary cancer, and that they might have an autocrine/paracrine role in the maintenance of this disease.     

Dissociated estradiol (E2) action on the pituitary-testicular axis in a genetically hypoprolactinemic rat (IPL nude rat)

Prolactin (PRL) has been reported to be a possible mediator in the estradiol (E2)-induced inhibition of the pituitary-testicular axis. In order to better characterize the role of PRL, we studied the action of chronic hypoprolactinemia on this E2 inhibitory effect, using a genetically hypoprolactinemic rat (IPL nude). Normal and IPL nude adult male rats were injected either with vehicle or with E2 valerianate (4 mg/rat) once a week for 2 weeks. Rats were decapitated 7 days after the last injection. Results showed that E2 increased, similarly in both strains, pituitary weight and serum PRL levels. Serum testosterone values were reduced by 96% in both strains. However, testis weight was significantly reduced by 30% in normal rat, while in IPL nude rat, no significant decrease was observed. PRL binding sites, expressed as fmol/mg protein, were reduced in normal rat by 40%. No decrease was found in IPL nude rat. The dissociated E2 action observed in IPL nude rat suggested that only testicular growth inhibition could be mediated by PRL and confirm that testosterone level decrease could be due to a direct action of E2 on Leydig cells.     

Senile dementia and Alzheimer's disease: A current view

Senile dementia, of which the most common cause is known as Alzheimer's disease, is a neurological disorder characterized clinically by memory and learning deficits. The disease may be shown to have a prevalence rate in the United States of greater than three per 1000 of the general population, and it may be shown that at any one time 600,000 individuals are affected by advanced stages of this disease. The disease, unique to man, is relentlessly progressive and refractory to treatment. In most cases, it is unrelated to cerebral vascular insufficiency, it is however associated with well defined morphological and biochemical changes at the cellular level. These include altered dendritic morphology, intracellular changes such as granulovacuolar and neurofibrillary degeneration, and extracellular deposits termed neuritic plaques. Moreover, a selective dysfunction in central cholinergic mechanisms has been demonstrated. Recent results from this laboratory have indicated that significant changes in chromatin conformation may be demonstrated to occur in this disease. Specifically, a significant “heterochromatization” was found to occur in chromatin from brains of patients who had died with this disease, suggesting that a major alteration in chromatin structure may be related to the etiology of this condition. In addition, an accumulation of the environmental agent aluminum upon brain cell chromatin has been implicated to contribute to the pathophysiology of Alzheimer's disease. During the past few years it has become possible to model several of the morphological markers of this disease in the laboratory. Specifically, the paired helical filament, representing a major intracellular marker can now be induced in cultured neurons and a filamentous hyperplasia similar to neurofibrillary degeneration, but not identical in morphology, may be induced in experimental animals and in neurons in vitro by trace amounts of aluminum. The understanding of Alzheimer's disease is in its infancy, however, the availability of model systems now permits extensive investigations into the nature and mechanisms of the agents responsible for the changes observed.     

Mapping of phase response properties of monopolar ECG voltages

In the present investigation an attempt has been made to study the phase response properties of monopolar chest lead ECG voltages. Using a generator model of the heart an equivalent circuit of ECG network has been developed. The equivalent impedance between WCT and probe electrode has been determined by reduction techniques. From this equivalent impedance the phasor characteristics of monopolar ECG voltages have been analysed for change in probe electrode locations. The source of the generated voltage, i.e., the heart, will develop a different voltage for its different condition. There will also be a change in impedances. Thus for the normal subject the distribution of the phasor of the ECG voltages will be different from that of the abnormal one. A software tool has been developed to evaluate the relative phase response of ECG voltages. The data acquisition of monopolar ECG records of chest leads V1 to V6 from chart recorder has been done with the help of AutoCAD application package. The harmonic constituents of ECG voltages have been evaluated at each harmonic plane and the phase characteristics have been studied in polar coordinate for normal subjects as well as for a typical case. An interesting result has been observed in typical cases which are indicated in the paper.     

Women's voice pitch lowers after pregnancy

Women's voice pitch (the perceptual correlate of fundamental frequency, F0) varies across the menstrual cycle and lowers after menopause, and may represent a putative signal of women's fertility and reproductive age. Yet, despite dramatic changes in women's sex hormone levels and bodies during and after pregnancy, previous between-subject and case studies have not found systematic changes in F0 due to pregnancy. Here, we tracked within-individual variation in 20 mothers' voices during their first pregnancy, as well as up to 5?years before conception and 5?years postpartum. Voice recordings from 20 age-matched nulliparous women were measured as a control. Linear Mixed Models indicated that F0 mean, range and variation changed significantly following pregnancy in mothers, controlling for age at time of recording, whereas we did not observe any F0 changes across corresponding timeframes in our sample of nulliparous controls. Mothers' voices became significantly lower-pitched and more monotonous during the first year postpartum compared to during pregnancy or before. These F0 parameters did not decrease within-individuals over a 5-year period prior to conception above and beyond the effects of ageing. Although voice pitch decreased following pregnancy, mothers' F0 parameters reverted after the first year postpartum, approaching pre-pregnancy levels. Our results demonstrate that pregnancy has a transient and perceptually salient masculinizing effect on women's voices.     

Abnormalities of lysosomes in human diploid fibroblasts from patients with Farber's disease

An accumulation of ceramide associated with the deficiency of acid ceramidase has been demonstrated in cultured diploid skin fibroblasts from a patient with Farber's disease. We extend this observation to investigate the lysosomal localization of accumulated ceramide and the abnormalities of lysosomes caused by this ceramide accumulation in Farber's diseased fibroblasts. We have found that the lysosomal fraction isolated from Farber's diseased fibroblasts by a subcellular fractionation procedure is markedly low in density compared with that of normal fibroblasts and is separated from other subcellular organellers. Ultrastructural studies of the isolated lysosomal fraction from Farber's diseased fibroblasts showed in mixed population of intact and swollen vesicles with a lysosomal appearance. Examination under high magnification clearly demonstrated lysosomal inclusions which contain lamellar and curvilinear membranes and resembled those seen in the intact fibroblasts. Subcellular localization of Farber's fibroblasts showed that the accumulated [³H]ceramide from the culture medium was predominantly localized in the lysosomal fraction with a markedly low density and very little was found to be associated with other cellular membranes. Our finding that ceramide is accumulated in the lysosomal fraction of Farber's fibroblasts and that these cells also show membranous inclusions strongly suggests that the accumulation of ceramide is directly involved in the formation of lysosomal inclusions.