The biochemical aspects of pineal gland functioning in the rat in ontogeny

We have studied metabolic pathways of serotonin in epiphysis of Wistar male rats at the age of 1; 1,5; 2; 3; 6; 12; 24 and 36 months. Epiphysis retains its functional activity throughout the life, however, serotonin metabolism in epiphysis undergoes marked changes. The main regulatory principle is the switch of serotonin metabolic pathways in the pineal gland. Most distinct changes between hydroxy- and methoxyindols in epiphysis have been observed during the periods of age-associated hormonal rearrangements like sexual maturation or involution of the gonad function at the old age.     

The effect of constant light and chemical sympathectomy on the development of serotonin, n-acetyltransferase and monoamine oxidase activities in the rat epiphyses.

The daytime activity of N-acetyltransferase per mg epiphysis decreased to 1/10 the newborn level by the age of 13 days, and subsequently remained unchanged. The night activity was equal to the day activity at the age of 3 days, was higher at the age of 6 days and was 20 X that of the day level at the age of 40 days. Keeping animals in constant light after birth depressed the development of these diurnal differences in N-acetyltransferase activity and slowed down the decrease in enzyme activity after birth. Sympathectomy with 6-hydroxydopamine after birth abolished the development of the diurnal rhythm in N-acetyltransferase in 12-day-old rats in two experiments out of five and only decreased the night activity without abolishing the rhythm in three experiments. Monoamine oxidase activity (MAO) per mg epiphysis, which is the same in newly born and in adult animals, decreased to half the original value for 6 days after birth and then increased again. Constant light after birth did not influence MAO activity, but sympathectomy with 6-hydroxydopamine decreased activity in the epiphysis in 12-day-old animals.     

Physiology of the epiphysis: Modern concepts

In this review, the information available from the literature and the data obtained by the author about the epiphysis (or the pineal gland), an important neuroendocrine organ, and about its main hormone, melatonin, are summarized. The history of studying the epiphysis and the evolutionary aspects of its activity, anatomy, and physiology are discussed. The results of electrophysiological studies are described, and biochemical aspects of the epiphysis activity are analyzed. The pathways through which photoinformation enters the pineal gland, and external factors regulating its functioning are described in detail. The data on the physiological effects produced by epiphyseal neurohormones (melatonin is the best studied) and their role in formation of different types of behavior are emphasized.     

Development of the cartilage canals and the secondary center of ossification in the distal chondroepiphysis of the prenatal human femur.

The cartilaginous epiphysis of the distal femur is vascularized by a network of cartilage canals during prenatal development. The vascular invasion of the epiphysis begins at approximately eight to ten weeks of gestation with the initiation of cartilage canal formation. A complex vascular system develops within the canals and is well defined by fourteen weeks of gestation. The vascular system is fully developed several months prior to the development of the secondary center of ossification. The formation of the secondary center of ossification within the distal femoral epiphysis is preceded by changes that occur simultaneously within both the chondrocytes in the central portion of the epiphysis and the vascular and perivascular elements contained within the cartilage canals in the central portion of the epiphysis. These concurrent changes in the cellular morphology of the central chondrocytes and in the cellular structure of the central cartilage canals appear to be linked with the initiation of the process of osteogenesis.     

Anatomo-histologic characteristics of the epiphysis of the female silver fox outside the breeding season

The epiphysis of mature relatively wild silver foxes of various age living in the fur-farming farm have been studied during November--December. The organ mass (2.72 +/- 0.14 mg) has rather essential individual differences and its statistically significant changes with age are not revealed. There are not any connective septa deviding parenchyma of the organ into lobules. There is also not any definite division between the cortex and medulla. Under all histological methods of treatment the borders of the parenchymal cells are poorly defined. Nuclei of the pinealocytes can be divided into light and dark according to their coloration. The average diameter of the nuclei in the pinealocytes does not practically change with age, nor does the linear density of cellular elements arrangement. A definite individual variability is noted in amount of the cells including secretory granules. The phenomena mentioned demonstrate that the fox epiphysis maintains its constant level of physiological activity during the whole reproductive period of life.     

Age-related changes in the serotonin content of the epiphysis of birds

Serotonin content of the epiphysis has been studied in 1-day chicks, 1-, 5-5 1/2-, 8-12- and 24-month hens. It was found that this content undergoes significant changes during life cycle of hens, being dependent on physiological activity of the gonads. The highest level of serotonin (16 micrograms/g) was observed in 8-12 months old hens which corresponds to the period of the most intensive activity of the gonads.     

Changes in activity levels of glutamate dehydrogenase and two transaminases of maternal liver during reproduction and after administration of oestradiol and progesterone in Zoarces viviparus (L.)

The enzyme activity per unit liver wet weight, the specific activity and the total liver activity level of glutamate dehydrogenase (GDH) and two transaminases (GOT and GPT) were studied during vitellogenesis and pregnancy. A steady level of activity was observed during the short summer vitellogenesis and during early pregnancy. During mid-term pregnancy in October the activity level significantly increased.
Administration of 5 and 100 μg oestradiol increased serum vitellogenin, total liver protein and the liver somatic index during late pregnancy. Oestradiol decreased activity and specific activity of the enzymes. However, expressing activity as total hepatic enzyme activity units in fish of standard body weight oestradiol had no effect.     

青蛙光敏感松果体神经节细胞自发放电的昼夜节律变化

为了研究青蛙松果体的昼夜节律,本实验采用细胞外连续记录,研究了松果体内对光产生抑制反应的光敏神经节细胞放电的昼夜节律变化.结果表明(1)所有表现自发放电的细胞,其放电频率介于1-6Hz之间,脉冲发放特征有规则、不规则(或波动)和阵发等方式;(2)无论在持续黑暗(DD)、持续光照(LL)或在模拟自然光照周期(L-D-L)任何一种条件下所进行的昼夜连续记录都显示:有些细胞在白天放电频率低,在夜间放电增强;而另一些细胞则在整个记录过程中,其脉冲频率基本上保持不变.当用与昼夜光照颠倒的周期(D-L-D)作实验时,所有被检测的细胞都反映出夜间的放电活性受到了不同程度的抑制.     

Serial estimation of serum angiotensin converting enzyme activity during and after pregnancy in a woman with sarcoidosis.

Serum angiotensin converting enzyme activities were estimated during pregnancy and the puerperium in a woman with sarcoidosis and a series of normal women. In the patient with sarcoidosis angiotensin converting enzyme activity was raised during pregnancy, particularly at 21 weeks'' gestation, yet she remained well with no symptoms to suggest relapse of sarcoidosis. Serum angiotensin converting enzyme activity may not be of value in monitoring sarcoidosis activity during pregnancy.     

Resumption of growth of heat inactivated embryonic epiphyses by grafting

Summary This communication describes a new experimental model for the study of the role of the extracellular matrix (ECM) in morphogenesis. In a preceding paper (Markson et al. 1991) we demonstrated that isolated epiphyses from femora of 6-day-old chick embryos grow during the first days in organ culture almost as well as their intact counterparts. Heating femora for 1 h at 45.2° C caused complete cessation of growth and proteoglycan biosynthesis. When the cut surface of a heat-inactivated (HI) epiphysis was brought into apposition with the cut surface of a live epiphysis and the attached pair placed in organ culture, the HI epiphysis began to grow and reached almost the same size as its live partner. The different possible interpretations of this finding are discussed. When a HI epiphysis of a certain shape (from humerus) is attached to a live epiphysis of a very different shape (from femur) and the attached pair is cultured for 6–7 days, the typical resumption of growth can be observed and the HI epiphysis that doubled or tripled its size retains its original characteristic form. The possibility that the existing infrastructure of the cartilaginous ECM directs the pattern of deposition of newly synthesized ECM by the chondroblasts is discussed, and it is suggested that stretch-activated channels participate in a process by which cells sense the topography of their ECM. Offprint requests to: F. Doljanski     

Detection of pregnancy in a hibernator based on activity data

Pregnancy and parturition are often difficult to detect in wild-living animals, especially in species that give birth to altricial young in burrows or caves. Current methods to detect pregnancy and birth in hibernating animals often entail disturbances that can affect the animals' reproductive success. We developed a new method to confirm pregnancy and parturition in hibernating brown bears (Ursus arctos) using activity data recorded in dual-axis motion sensors mounted on GPS–GSM neck collars on 30 brown bears during 52 hibernation seasons in Sweden. We adjusted recorded activity to the individual basal activity level for each bear. Pregnant females showed characteristic activity patterns during the period of pregnancy, with significantly higher daily activity levels and frequency of active periods during pregnancy than nonpregnant bears. Pregnant females were active on average 2.20 times more often during the pregnancy period than during the postpartum period, compared with 0.97 times for nonpregnant females. A pregnancy index was defined as the average of the proportion of mean daily activity levels and the proportion of activity events during the pregnancy period compared with the postpartum period. It averaged 2.61?±?1.73 (SD) for pregnant females and 0.94?±?0.24 for nonpregnant females. Using this method, we evaluated a group of adult females that had an unverified reproductive status but were classified as not pregnant because no cubs had been observed after den emergence. The results suggested that 35 % of those females had, in fact, been pregnant.     

Slipped Capital Femoral Epiphysis In a Patient With Turner Syndrome Receiving Growth Hormone Therapy

ObjectiveTo report a case of slipped capital femoral epiphysis in a young patient with Turner syndrome (TS) receiving growth hormone therapy and to emphasize the importance of keeping this orthopedic condition in mind during management of this patient group.MethodsClinical, laboratory, and radiographic findings are presented, and risk factors for slipped capital femoral epiphysis are discussed.ResultsA child with TS presented for medical assessment because of a limp but with no history of trauma or febrile illness. Growth hormone therapy had been administered for 1 year because of her short stature. Physical examination and pelvic radiography of the patient showed the presence of bilateral slipped capital femoral epiphysis. She underwent bilateral pinning in situ, and growth hormone therapy was terminated. At follow-up after more than 2 years, no sequelae were noted.ConclusionPatients with TS are at high risk for developing certain orthopedic conditions, such as slipped capital femoral epiphysis. Furthermore, slipped capital femoral epiphysis is a known complication of growth hormone therapy in growing children. A limp, hip pain, knee pain, or thigh pain might be a symptom of slipped capital femoral epiphysis in patients with TS, especially those receiving growth hormone therapy. Prompt recognition and treatment of this condition are important for prevention of sequelae. (Endocr Pract. 2012;18:e135-e137)     

Effect of the epiphysis and hypophysis on the circadian organization of the wakefulness-primary sleep cycle in the frog Rana temporaria

Using continuous non-contact registration of the heart rate and motor activity in unrestrained frogs, studies have been made of the effects of hypophysectomy and epiphysectomy on functional state of the organism. It was shown that removal of the epiphysis alleviates the circadian physiological rhythm of natural changes of functional states in wakefulness-primary sleep cycle, whereas removal of the hypophysis results in additional cyclic rhythm of two functional states in the diurnal periodicity of the behaviour. The latter effect is considered to be the ultradian rhythm, which in the intact animals is masked by the circadian one modulated by natural diurnal illumination. It is suggested that removal of the epiphysis reveals endogenous rhythm of the activity typical of periodic regimes of the spontaneous excitation at early stages of ontogenesis.     

Late pregnancy suppresses relapses in experimental autoimmune encephalomyelitis: evidence for a suppressive pregnancy-related serum factor

Women with multiple sclerosis have significantly diminished disease activity during pregnancy. The purpose of our study was to identify the underlying mechanism for the diminished disease activity. We found that during the period of late pregnancy there is protection against paralysis, during both the induction and effector phases of relapsing experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. We did not find any changes in the cytokine secretion profiles or the proliferative activity of autoreactive T cells from mice induced during late pregnancy compared with virgin controls. In mice mated after disease onset, the inflammatory histologic lesions did not clear, despite marked clinical improvement during pregnancy. We found evidence for a serum factor present in late pregnancy that suppresses T cell activation. In the presence of sera taken from mice late in pregnancy, the proliferative response and IL-2 production of proteolipid protein p139-151-specific T cells were significantly diminished as compared with stimulation in the presence of normal mouse sera. In conclusion, serum from late pregnancy has the capacity to down-regulate T cell responses and might be associated with the amelioration of disease activity in experimental autoimmune encephalomyelitis.     

ACE2 expression and activity are enhanced during pregnancy

In the current study, we investigated the expression and activity of ACE2 during pregnancy in normotensive and hypertensive rats, focusing on the relative contribution of the uterus and the placentas, the kidney serving as a reference. We used the Sabra rat model of salt-sensitive hypertension. We confirmed a systemic vasodilatory state during the third trimester of pregnancy, as evidenced by a reduction in blood pressure, both in normotensive and hypertensive rats. At the time that blood pressure was reduced, ACE2 was expressed abundantly in the reproductive organs. The relative levels of ACE2 mRNA in the pregnant animal were placenta > kidneys > or = uterus and of ACE2 activity kidney > placenta > uterus. In the uterus and the placenta, ACE2 expression was unaffected by strain, salt-loading, or the level of blood pressure. ACE2 activity in the uterus of the nonpregnant rat was not affected by any of these variables either, but during pregnancy increased in salt-loaded animals. When estimating the total contribution of the uterus to ACE2 mRNA and activity during pregnancy, we found that the amount of ACE2 mRNA increased in both strains irrespective of diet, but that ACE2 activity increased only in salt-loaded animals. We further estimated the relative total contribution of the uterus, placentas, and kidneys to ACE2 expression and activity during pregnancy by adjusting for mass and number of organs and found that the placentas were the major contributors, followed by the kidney and the uterus. We conclude that during pregnancy, the placentas, in particular, but also the uterus, constitute important sources of ACE2, in addition to its normal production in the kidney, leading to an estimated twofold increase in total ACE2 activity. These data are consistent the hypothesis that transient ACE2 overexpression and increased activity during pregnancy may be important in modulating systemic, as well as local hemodynamics in the uteroplacental unit.     

Factors Related to Body Weight Changes During and After Pregnancy: The Stockholm Pregnancy and Weight Development Study

The Stockholm Pregnancy and Weight Development Study is a prospective study of body weight changes in women, whose maternity unit charts were reviewed and who were then invited for a 1-year follow-up, including weigh-in sessions and questionnaires on dietary habits, physical activity and socio-demographic factors. Total weight gain during pregnancy was related to weight gain already during the first trimester. Women reporting previous weight cycling had slightly higher weight gain during pregnancy. Successful return towards pre-pregnancy weight was found more often in women with regular breakfast and lunch habits. Lactation had only a small effect on weight loss after delivery, independent of eating habits. Lack of physical activity was more common in women who had low lactation scores. Twenty-eight percent reported an increased interest in sweets during pregnancy; these women increased 1 to 2 kg more than others in weight during pregnancy. Postpartum weight retention was more affected by lifestyle changes during and after pregnancy than by factors before pregnancy.     

Adipose tissue metabolism during early pregnancy in the rat: temporal relationships of changes in the metabolic activity, number of insulin receptors, and serum hormone concentrations

The temporal relationships between changes in rates of fatty acid and acylglycerol glycerol synthesis; the activity of lipoprotein lipase of parametrial adipocytes and their capacity to bind insulin; and the serum concentrations of insulin, progesterone, prolactin, and total lactogenic activity have been examined in rats during the first 15 days of pregnancy. The rate of fatty acid and acylglycerol synthesis showed a transient increase at Days 9 and 12 of pregnancy, whereas there was no change in the activity of lipoprotein lipase activity except for a fall between Days 12 and 15 of pregnancy. The capacity of adipocytes to bind insulin was increased by Day 6 of pregnancy and remained elevated until at least Day 15; no changes in the affinity for insulin were observed. Serum progesterone, insulin, and total lactogenic activity were elevated by Days 3, 9, and 12 of pregnancy, respectively. The results show that progesterone but not placental lactogen could be responsible for the rise in the insulin-binding capacity of rat adipocytes during pregnancy, whereas the fall in lipogenic capacity at about Day 12 of pregnancy coincides with the rise in serum placental lactogen.     

Changes and localization of ovarian carbonyl reductase during pseudopregnancy and pregnancy in rats

The present study investigates changes in the activity and enzyme content of ovarian carbonyl reductase (CR), which catalyzes the reduction of 9-keto and 15-ketoprostaglandins in rats during pseudopregnancy and pregnancy. The activity of ovarian CR decreased from the onset of pseudopregnancy and pregnancy, reaching 20-30% of the Day 1 value by Day 12 of pseudopregnancy and 50-60% of the Day 1 value by Day 14 of pregnancy. In the case of pregnant rats, the enzyme activity maintained a minimal level between Day 14 of pregnancy and Day 22 of parturition. An acute increase of the enzyme activity was found on the morning after parturition. The CR content in the ovary maintained a constant level from Day 1 to Day 12 of pseudopregnancy and to Day 18 of pregnancy. In pregnant rats, there was a gradual decrease after 18 days and then a surge during parturition. CR was primarily localized in interstitial gland cells and in theca interna cells but was not found in corpora lutea cells in the ovary during the estrous cycle. Additional immunostaining was also observed in corpora lutea cells during pseudopregnancy and pregnancy. The changes in ovarian CR activity, i.e. the rapid decrease with progressing pseudopregnancy and pregnancy, correlated with the increase in progesterone and the decrease in LH. These results indicate that rat ovarian CR may be regulated via the hypothalamo-pituitary-ovarian axis and may also be involved in luteal function.     

Developmental expression of zebrafish emx1 during early embryogenesis

Emx family homeobox genes, Emx1 and Emx2, play an essential role in rostral brain development in mammalian embryos. Here we report a zebrafish emx family gene, emx1, which is more similar to the mouse Emx1 gene than the previously reported zebrafish emx1 gene; we propose to rename that gene emx3. The expression of emx1 is first detected around the 10-somite stage in the pineal gland (epiphysis) primodium in the developing anterior brain and in the pronephric primodium within the intermediate mesoderm. emx1 expression in the epiphysis has not been reported in other species. Expression in the epiphysis is suppressed at 23 h post-fertilization (hpf) in the floating head (flh) mutant, in which development of the epiphysis is impaired. Subsequently, emx1 is expressed in the telencephalon, as reported in mammals, and can be detected in the olfactory placode and in a small group of cells in the forebrain at 25 hpf. In the mesoderm, emx1 expression is gradually concentrated in the posterior pronephric duct during somitogenesis, and becomes expressed predominantly in the urogenital opening at 25 hpf. Thus, emx1 displays a unique expression pattern that is distinct from the patterns of emx2 and emx3.     

The potential role of variations in juvenile hip geometry on the development of Legg-Calvé-Perthes disease: a biomechanical investigation

Legg-Calvé-Perthes disease (LCP) is one of the most poorly understood diseases in paediatric orthopaedics. One common trait of LCP is the marked morphological difference between healthy and pathological hips, early deviations of which (i.e. prior to disease onset) have been suggested to lead to the overload and collapse of the epiphysis. Here, the impact of common variations in geometry is investigated with a finite element model of a juvenile femur under single leg standing and landing. Here, the impact of typical variations in geometry is investigated with a finite element model of a juvenile femur under single leg standing and landing. The variations appear to have only a limited effect on the stress distribution in the femoral epiphysis even during high impact activities. This suggests that, for this individual at least, they would be unlikely to cause epiphyseal overload and collapse, even in the presence of a skeletally immature epiphysis.