Gonadal and adrenal endocrine functions in female minks of 2 genotypes in postnatal ontogeny

Radioimmune assay has been made of the content of estradiol and progesterone in the blood (from July to March including the 7th day after mating), as well as on the level of estradiol and progesterone production in young females of the standard and mutant sapphire minks in November. It was shown that within certain periods, estradiol and progesterone content of the blood was significantly higher in the standard animals. Gonadal production of estradiol, as well as progesterone production both by the gonads and adrenals in November, were similar in females of both genotypes. It is suggested that sapphire minks have another pattern of correlation between estradiol content of the blood and gonadal production of estradiol as compared to that in standard animals.     

Maternal thyroid function in early and late pregnancy.

Thyroid function was investigated during and after pregnancy in 12 healthy euthyroid women. During pregnancy, serum total T4 (TT4) levels were significantly elevated and nearly stable, while thyroxine-binding globulin (TBG) levels progressively increased till the 7th month. A slight elevation, though not significant, of free T4 (fT4) was recorded in early pregnancy. In the following months, fT4, free T3 (fT3) and the T4/TBG ratio progressively diminished, reaching a plateau at the 7th month. Serum TSH levels, measured by an ultrasensitive immunofluorometric assay, were comparable to postpartum values during the first trimester and showed a moderate upward trend with the progression of pregnancy. The evaluation of 24-hour TSH profiles was performed in 5 women during the first trimester of pregnancy. In all women, the circadian rhythm of TSH was present with a normal nocturnal surge, though anticipated in 1 case. In summary (1) during the first trimester of pregnancy, the increased thyroid activity does not seem to be only sustained by pituitary TSH which remains unmodified; the negative correlation between TSH and hCG levels might suggest that hCG also stimulates the gland to increase thyroid hormone output, and the presence of a normal TSH circadian rhythm indicates that the central mechanism of neuroregulation of the pituitary-thyroid axis is preserved in early pregnancy, and (2) in late pregnancy, a marked decrease in free thyroid hormone fractions is accompanied by serum TSH levels still in the normal range, indicating a modification of thyroid homeostasis which might recognize various etiological factors.     

Pleiotropic effect of the Black crystal mutation on reproductive indicators in the American mink (Mustela vison)]

The parameters of reproduction were studied in American minks that were homo- and heterozygous for the Black crystal mutation (Cr). The given mutation that changes the hair pigmentation was obtained de novo duration selection of American minks for tame behavior. Apart from changed color, the following reproduction disorders were detected in the Black crystal mutants, as compared to standard animals: (1) delayed entry into the reproductive season in females; (2) greater percentage in both homo- and heterozygous animals of females bearing no offspring; (3) greater early postnatal lethality indices. The most marked suppressing effect on the development of offspring was detected in homozygous females (Cr/Cr), whose progeny perished within a few days after birth. An analysis of reproduction in mutants and standard animals is presented. An attempt was made to explain the conceivable mechanisms that form the basis of disorders detected.     

Hyperthermia and increased physical activity in the fasting American mink Mustela Vison

The aim of this study was to investigate the thermoregulatory adaptations to fasting in a medium-sized mustelid with a high metabolic rate and energetic requirements. Sixteen farm-bred female American minks, Mustela vison, were divided into a fed control group and an experimental group fasted for 5 days. The deep body temperature (T(b)) of the minks was registered at 10 min intervals with intraabdominal thermosensitive loggers and the locomotor activity was videotaped continuously for 5 days during the fasting procedure. The T(b) of the fasted animals increased during the first day of fasting and decreased during the second day. After 3-4 days of fasting, the levels of physical activity and T(b) of the fasted minks increased above the levels of the fed animals. Significant increases in these parameters were observed at the beginning of the working day on the farm, during the feeding of the fed animals and around midnight. It is concluded that the mink differs from previously studied homeotherms in thermoregulatory and behavioral responses to fasting probably due to its high energy requirements and predatory success.     

Compensatory-restorative processes of the thyroid gland in 1- and 3-month-old rats in health and in desympathization

In 172 white male rats 1- and 3-month-old, using electron microscopical, autoradiographical, morphometrical and radioimmunological methods, analysis of structural-functional changes of the thyroid gland has been carried out both under normal conditions and at guanethidine desympathization (15 mg/kg for 14 days after birth). Resection of 2/3 of the organ has been performed on the 3d, 5th, 7th and 15th days before sacrifice. In the 1-month-old desympathized rats hypofunctional state of the gland is observed. By the 3d month at the expense of an increased production of thyrotropin and calcitonin the thyroid status becomes normal. The dynamics of the restorative processes in the thyroid gland after resection of 1/3 of the organ in the control and test rats occurs with a similar intensity. Proliferative potency of the desympathized thyroid tissue is much higher.     

Piperine lowers the serum concentrations of thyroid hormones, glucose and hepatic 5'D activity in adult male mice.

Piperine, the main alkaloid of Piper nigrum fruits, was evaluated for its thyroid hormone and glucose regulatory efficacy in adult male Swiss albino mice. Its daily oral administration (2.50 mg/kg) for 15 days lowered the serum levels of both the thyroid hormones, thyroxin (T (4)) and triiodothyronine (T (3)) as well as glucose concentrations with a concomitant decrease in hepatic 5'D enzyme and glucose-6-phospatase (G-6-Pase) activity. However, no significant alterations were observed in animals treated with 0.25 mg/kg of piperine in any of the activities studied except an inhibition in serum T (3) concentration. The decrease in T (4), T (3) concentrations and in G-6-Pase were comparable to that of a standard antithyroid drug, Proylthiouracil (PTU). The hepatic lipid-peroxidation (LPO) and the activity of endogenous antioxidants, superoxide dismutase (SOD), and catalase (CAT) were not significantly altered in either of the doses. It appears that the action of P. nigrum on thyroid functions is mediated through its active alkaloid, piperine. We also suggest that a higher dose of piperine may inhibit thyroid function and serum glucose concentration in euthyroid individuals.     

Deiodination in the kidney and thyroid function)]

In homogenate supernatants of kidneys of male rats the extent of deiodination of L-diiodotyrosine (L-DJT) and L-thyroxine (L-T4) was investigated in dependence on the thyroid function (hypo- and hyperthyroidized) and also in dependence on age. In rats hypothyroidized by loading with Methylthiouracil (MTU) or Methimazol (MMI) the deiodination for L-DJT and L-T4 was significantly reduced, in rats loaded with 40 mug T4 sc. for 10 days, the deiodination was significantly enhanced compared with untreated control animals. With advancing age (6 weeks, 3 or 12 month) the deiodination activity is highly significantly reduced. The results underline relations between thyroid gland function and deiodination activity in kidney.     

Estrous Cycle,Folliculogenesis, and Brain Catecholamines after Stimulation of the Sexual System by Choriogonadotropin in Female Minks Selected for Behavior

The content of hypothalamic dopamine (DA) and noradrenaline (NA) is determined and ovary function (folliculogenesis) in various states of estrous cycle is studied in non-selected (control) immature (7-month old) standard female minks and in similar females of aggressive and quiet behavioral types (the 18th generation of selection) in norm and at the 7th day after single intramuscular injections of chorionic gonadotropin (CG). At the 7th day after the CG administrations, the control females were distributed by their estrous cycle state as follows: anestrus (A)— 47.2%, anestrus-proestrus (AP)—10.0%, proestrus (P)—8.5%, proestrus-estrus (PE)—14.3%, and estrus (E)— 20.0%. In the female minks selected for behavior, there was a significant increase of percentage of estrous females: to 84.6% in the aggressive ( p < 0.001) and to 58.4% in the quiet type animals ( p < 0.01). The number of growing and maturing (at the early stage) follicles in intact females of aggressive behavior was lower than in control and in females of the quiet type. However, the number of Graafian vesicles in ovaries of aggressive and quiet females did not differ and exceeded control. The stimulation by CG enhanced the differences between the ovaries of selected animals. In control females at the 7th day after CG injections there was a tendency for a decrease of the DA and NA content with development of estrus (A→AP→P). The hypothalamic DA concentration was higher in intact females of the aggressive type than in the quiet females ( p < 0.05). In animals of the aggressive type, stimulation of the sex system decreased the DA level. No correlation between sexual function and DA and NA levels was found in females of the quiet type. However, differential analysis of NA in these females with different reactions of vaginal epithelium to CG stimulation (A, AP vs P, PE, E) indicates correlation of catecholamine level with sexual function. Thus, selection of minks for aggressive behavioral type produces an increase of the hypothalamic catecholamine level, which, in turn, is one of factors inhibiting sexual function.__________Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 3, 2005, pp. 266–271.Original Russian Text Copyright © 2005 by Klochkov, Alekhina, Trapezov, Petrenko.     

Study of Exploratory Behavior in the European Mink (<Emphasis Type="Italic">Mustela lutreola</Emphasis>)

The European mink (Mustela lutreola) is among the most endangered mammals in Europe and has been assigned with the CR (Critically Endangered) status. In Russia the European mink has disappeared from most of its former range; its population is extremely small. In the near future it will need to be reintroduced into former habitats using captive-raised animals. This work investigates exploratory behavior of captive- raised European minks. The research was conducted in the nursery of the European mink in the Ilmen Nature Reserve. Thirty captive-raised European minks of different ages (from 4.5 months up to 7 years; 17 females and 13 males) participated in the experiments. It has been shown that European minks who have lived in cages or enclosures for several generations continue to exhibit pronounced dispersion of exploratory behavior parameters. They have maintained the ability to quickly explore unfamiliar territory and find shelter. There are no differences between males and females in the length of distance covered in the test. Age does not affect the activity of mink with respect to exploration of the territory and finding shelter. Differences in activity and division into groups according to the number of crossed squares within the sexes were determined by the personality of the minks. Individual features of behavior prevailed over group characteristics (sex and age). Despite continuous contact with the staff, most minks did not acquire adaptation to people.     

Brain monoamine oxidase in mink selected for their reaction to man]

Monoamineoxidase activity was studied in minks of three behavioural groups--those bred for absence of aggression towards man, those bred for high aggression to man, and those of non-selected population. Breeding for the absence of aggression was accompanied by a decrease of MAO-B activity with unchanged MAO-A activity. The minks bred for aggressive behaviour towards man, as compared to those bred for the absence of aggression, were characterised by increased MAO-A and MAO-B activities in the brain stem. The effect of emotional stress on MAO-A and MAO-B was similar in aggressive, non-aggressive and unselected minks and was expressed in a decrease of both MAO-A and MAO-B activity. The MAO activity of cerebral hemispheres remained unaffected both by selection for behaviour and by the emotional stress.     

Relevance of increased serum thyroxine concentrations associated with normal serum triiodothyronine values in hypothyroid patients receiving thyroxine: a case for "tissue thyrotoxicosis".

Fifteen patients receiving standard thyroxine replacement therapy (100-200 micrograms daily) for primary hypothyroidism and who had persistently raised free thyroxine concentrations in their serum were investigated to see whether the dose being given was too high. In addition to the usual thyroid hormone assays systolic time intervals (which indicate left ventricular contractility) were calculated as accurate reflectors of tissue thyroid activity. All patients showed the expected increased free and total thyroxine concentrations; but mean total and free concentrations of triiodothyronine were normal, while reverse triiodothyronine values were raised. Mean systolic time intervals were significantly reduced as compared with normal and fell within the thyrotoxic range. Seven patients subsequently had their doses of thyroxine reduced by 50 micrograms daily and were reinvestigated one month later. All showed significant falls in circulating thyroxine and triiodothyronine concentrations and an increase in mean systolic time intervals to the normal range. In patients receiving thyroxine replacement therapy for primary hypothyroidism a raised serum thyroxine concentration may indicate tissue thyrotoxicosis and should prompt a reduction of the thyroxine dose.     

Effect of mutations affecting coat color on the blood lymphocyte structure in the American mink (Mustela vison Schreber, 1777)

American minks with different genotypes containing the Aleutian coat color allele in the homozygous state, including the single recessive Aleutian (a/a); double recessive sapphire (a/a p/p) and lavender (m/m a/a); triple recessive violet (m/m a/a p/p); and dominant-recessive cross sapphire (S/+ a/a p/p), sapphire leopard (S(K)/+ a/a p/p), and shadow sapphire (S(H)/+ a/a p/p) minks, as well as American minks without the Aleutian allele, including the standard (+/+); single recessive silver-blue (p/p) and hedlund-white (h/h); double recessive pearl (k/k p/p), Finnish topaz (t(S)/t(S) b/b); incompletely dominant royal silver (S(R)/+), standard leopard (S(K)/+), and black crystal (C(R)/+); and dominant-recessive snowy topaz (C(R)/+ t(S)/t(S) b/b) and Kujtezhy-spotted (S(K)/+ b/b) minks have been studied. Homozygosity for the a allele has been found to disturb the subcellular structure of leukocyte, namely the formation of abnormally large granules.     

Therapeutic exploration of betulinic acid in chemically induced hypothyroidism

Hypothyroidism is a chronic condition characterized by abnormally low thyroid hormone production. The decreased serum level (>5.1 mIU/l) of thyroid-stimulating hormone (TSH) in blood indicates hypothyroidism. The study was an attempt to access the effect of betulinic acid on chemically induced hypothyroidism in female albino rats. Betulinic acid is a naturally occurring pentacyclic triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as anticancer potential, by inhibiting topoisomerase. Hypothyroidism was induced in female albino rats using propylthiouracil (PTU) at a dose of 60 μg/kg body weight orally for 1 month. Induction of hypothyroidism was confirmed by increased TSH level. At the end of second month, blood was collected, centrifuged and serum was analyzed for TSH, T3, and T4 level and protocol was terminated by killing of animals. The animals exposed to PTU were treated with pure standard drug thyroxine at a dose of 10 μg/kg of body weight by oral route and the test drug betulinic acid 20 mg/kg by oral route through force feeding in their respective groups. Treatment was carried out for a period of 2 months. Group with PTU-induced hypothyroidism showed an elevation in serum TSH and reduction level, which was restored by the betulinic acid in treated female albino rats. Betulinic acid also reduced the damage caused in the thyroid tissues by PTU, thus minimizing the symptoms of hypothyroidism. Histopathological examinations of the thyroid tissue showed changes in the thyrocytes of PTU-treated group while thyroxine group showed normal thyroid follicles cell architecture and the group treated with betulinic acid also showed marked improvement in the follicles integrity which shows that betulinic acid has some protective activity. This study shows that the betulinic acid has thyroid-enhancing potential by lowering down the TSH levels and reducing the damage caused in the thyroid tissues, thus minimizing the symptoms of hypothyroidism when used anaphylactically in rats.     

Effect of physical conditioning on measures of thyroid hormone action

Serum thyroid function tests (T4, T3, rT3 and TSH levels) and measures of peripheral thyroid hormone action (serum dopamine-beta-hydroxylase activity (DBH) and sex hormone binding globulin (SHBG] were determined in 6 women before and one month after initiating an aerobic physical conditioning program. The same measurements were made in a control group of 6 women who did not increase their activity during this time. In physically conditioned subjects, the resting heart rate decreased from 65.1 +/- 3.9 (mean +/- SE) at baseline to 58.0 +/- 2.9 beats per minute after one month (P less than 0.025), indicating an appreciable state of physical conditioning was achieved. However, there were no statistically significant changes in thyroid function test, serum DBH or SHBG levels in either the physically conditioned or the control group. These data indicate that being physically conditioned has a negligible effect on thyroid status.     

Serum thyroid hormone profile and trace elements in children receiving valproic acid therapy: A longitudinal and controlled study

Valproic acid (VPA) may affect thyroid hormone profile, causing alteration in serum trace elements concentrations. The aim of this study was to prospectively investigate this relationship in children receiving VPA monotherapy for a period up to 6 months. Serum thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroxine (T4), triiodothyronine (T3), thyroglobuline (TG), selenium (Se), zinc (Zn), and copper (Cu) levels were evaluated at baseline and at the 6th month in all the patients and in the control group. The mean Cu concentration in the 6th months of VPA therapy was significantly lower than that of the control group. TSH level was significantly increased in the patient group whereas FT4 was significantly decreased. The mean TSH level in the 6th month of VPA therapy was significantly higher than that of the control group, whereas mean T4 level was significantly lower. The Cu level in the 6th months of VPA therapy was positively correlated with T4 level. Δlog Cu and ΔTSH were negatively correlated. This study suggests that the alteration in the serum thyroid hormone profile during VPA therapy may result from the reduction in serum Cu levels.     

Detection, analysis and interactions of plasma ghrelin, leptin and growth hormone in the mink (Mustela vison)

The aim of this study was to obtain basic knowledge of the plasma concentrations and interactions of weight regulatory hormones in juvenile minks (Mustela vison). Ghrelin, leptin, and growth hormone (GH) levels were validated and determined by radioimmunoassay methods from the plasma of 30 female and 30 male minks. The female minks had higher plasma ghrelin and GH levels than the males. The plasma ghrelin concentrations of the females correlated positively with their body masses (BMs). The plasma leptin levels did not differ between sexes, but there was a positive correlation between the plasma leptin concentrations and BMs in the male minks. When the data from the male and female minks were combined, the correlation between the leptin levels and the BMs was still clear, but this was not observed in the females alone. In the male minks, the plasma GH levels correlated positively with the BMs and with the plasma leptin concentrations. However, there was no correlation between the plasma ghrelin and GH or leptin concentrations. The hormone concentrations were quite similar to earlier measurements in other carnivores.     

Interplay between aggression,brain monoamines and fur color mutation in the American mink

Domestication of wild animals alters the aggression towards humans, brain monoamines and coat pigmentation. Our aim is the interplay between aggression, brain monoamines and depigmentation. The Hedlund white mutation in the American mink is an extreme case of depigmentation observed in domesticated animals. The aggressive (?2.06 ± 0.03) and tame (+3.5 ± 0.1) populations of wild‐type dark brown color (standard) minks were bred during 17 successive generations for aggressive or tame reaction towards humans, respectively. The Hedlund mutation was transferred to the aggressive and tame backgrounds to generate aggressive (?1.2 ± 0.1) and tame (+3.0 ± 0.2) Hedlund minks. Four groups of 10 males with equal expression of aggressive (?2) or tame (+5) behavior, standard or with the Hedlund mutation, were selected to study biogenic amines in the brain. Decreased levels of noradrenaline in the hypothalamus, but increased concentrations of the serotonin metabolite, 5‐hydroxyindoleacetic acid and dopamine metabolite, homovanillic acid, in the striatum were measured in the tame compared with the aggressive standard minks. The Hedlund mutation increased noradrenaline level in the hypothalamus and substantia nigra, serotonin level in the substantia nigra and striatum and decreased dopamine concentration in the hypothalamus and striatum. Significant interaction effects were found between the Hedlund mutation and aggressive behavior on serotonin metabolism in the substantia nigra (P < 0.001), dopamine level in the midbrain (P < 0.01) and its metabolism in the striatum (P < 0.05). These results provide the first experimental evidence of the interplay between aggression, brain monoamines and the Hedlund mutation in the American minks.     

Premature induction of glucokinase in the neonatal rat by thyroid hormone.

1. It was shown that the development of liver glucokinase in the rat coincided with a peak in the levels of circulating thyroid hormone at about the 16th postnatal day. 2. Administration of thyroid inhibitors blocked the development of the enzyme and administration of thyroid hormone restored activity to normal levels. 3. Glucokinase could be induced prematurely as early as the 2nd postnatal day by the administration of thyroid hormone followed by daily injection of glucose (10 mg/g body weight). 4. Glucocorticoids and corticotropin failed to induce glucokinase activity prematurely. 5. The postnatal increase in circulating thyroid hormone levels together with increased intake of carbohydrate at weaning may be the normal physiological stimulus for induction of this enzyme.     

Effect of coat color mutations on behavioral polymorphism in farm populations of american minks (Mustela vison Schreber, 1777) and sables (Martes zibellina Linnaeus, 1758)

Behavioral polymorphism estimated by the expression of the defensive reaction towards humans has been studied in farm-bred American minks and sables with different color types. Most animals (both minks and sables) from farm populations displayed passive defensive behavior towards humans in the standard hand catch test. Coat color genes have been found to have pleiotropic effects; they influence both the penetrance and expressivity of domestication behavior: in animals with aberrant color types (both sapphire minks and white-and-black sables), the proportion of animals with domestication behavior and the expressivity of this behavior are significantly higher (p <0.01 and p < 0.001, respectively).     

Thyroid gland activity and motor activity during dog ontogenesis]

The locomotor activity (LA) and the level of the protein-bound iodine (PBI) in the blood serum were investigated in 62 puppies at the age of 1--12 months. A parallel elevation of PBI and the LA was observed the first 4 months after birth. The second peak of the LA at the age of 7--9 months was not accompanied by any PBI rise. Inhibition of the thyroid function with mercasolyl increased the LA at the age of 1--3 months and decreased it at the age of 7 months. An increase of the LA one month after thyroidectomy was found at the age of 1 and 3.5 months. The activity of puppies operated on at the age of one month showed a sharp fall after 2--4 months. The data on various effect of thyroid hormones on puppies of different age pointed to the complex relation between the LA and the thyroid gland function.