Thoughts on the causes of seasonality of menarche

The pineal gland plays an important role in the production of melatonin and in the synchronization of the reproduction process in seasonal breeding animals. Changes in the duration of day length are the most important stimulatory factors. In humans the pineal gland may not only have a physiological role in the seasonality of maturation, but also concerning the simultaneously observable changes of serum hormone and serum melatonin levels as well as in regard of changes in hair colour in prepuberal children. Therefore the pineal gland seems to play an important physiological role in the timing of human maturation.     

The thyroid and photoperiodic control of seasonal reproduction in American tree sparrows (Spizella arborea)

To explore the role of the thyroid gland in the control of seasonal reproduction in obligately photoperiodic American tree sparrows (Spizella arborea), the effects of (1) thyroxine administered in drinking water to thyroid-intact photosensitive or photorefractory birds, and (2) radiothyroidectomy before and after photostimulation and during photorefractoriness were examined. Chronic administration of pharmacological doses of thyroxine induced testicular growth and usually regression in initially photosensitive birds held on short or intermediate daylengths. Some thyroxine-treated birds with regressed testes were absolutely photorefractory, but most remained photosensitive. Exogenous thyroxine never induced testicular growth in photorefractory birds moved to short days, though it often impeded, and sometimes even blocked, the recovery of photosensitivity. Although circumstantial, these effects of exogenous thyroxine are consistent with an hypothesis that assigns to thyroid hormones two roles — one stimulatory and the other inhibitory — in the control of seasonal reproduction. Radiothyroidectomy before photostimulation inhibited (but did not prevent) photoinduced testicular growth, blocked spontaneous testicular regression, suppressed molt, and prevented photorefractoriness. Moreover, as demonstrated by testicular growth after thyroxine replacemnt therapy, radiothyroidectomy during photorefractoriness later restored photosensitivity despite continued photostimulation. Thus, euthyroidism is an essential condition for maximizing (but not for initiating) photoinduced testicular growth and for triggering and maintaining photorefractoriness in photostimulated tree sparrows. However, when performed early during photostimulation, radiothyroidectomy neither immediately induced nor later blocked spontaneous testicular regression. Thus, endogenous thyroid hormones and long days may interact during a critical period to program a sequence of physiological events that plays out as photorefractoriness in chronically photostimulated birds. Such an organizational event cannot be permanent, for seasonal reproduction is episodic and its control mechanism necessarily cyclic. Because thyroidectomy simulated the well-known restorative effect of short days (and exogenous thyroxine impeded it), short days may dissipate photorefractoriness by creating a milieu wherein thyroid hormones are deficient or inactive.Abbreviations ANOVA analysis of variance - bTSH bovine thyroid stimulating hormone - GnRH gonadotropin-releasing hormone - LH luteinizing hormone - nL: nD daily light: dark regime (n is duration in hours) - SEM standard error of the mean - SNK Student-Newman-Keuls test - T₄ thyroxine - TH thyroid hormone - TR thyroid hormone receptor     

Assaying progesterone,estradiol and cortisol concentrations in hair of Père David deer hinds: an alternative way to reflect seasonality of steroid secretion

The use of a hair hormone concentration assay is increasingly recognized as a useful and noninvasive technique for monitoring the endocrinological status of animals. However, few studies have focused on reproductive and stress hormones together. We used a chemiluminescent immunoassay to determine whether the progesterone, estradiol, and cortisol concentrations could be measured from hair and whether these hormone concentrations varied in different hair segments of captive Père David deer hinds. We found that progesterone, estradiol, and cortisol could be measured in the hair samples and that the progesterone concentration varied but the estradiol and cortisol concentrations did not among different hair segments. Contrary to the segmental decline in hair cortisol found in many studies, we found that progesterone concentration was higher near the tip than at the base of hair in Père David deer. This suggests that the variation in segmental hair steroid hormone concentration in seasonal molting animals may be mainly due to internal reproductive cycles and that hair steroid hormones may reflect long-term physiological changes and can thus be used for the conservation and management of wildlife.     

Melatonin Modulates Thyroid Hormones and Splenocytes Proliferation Through Mediation of Its MT1 and MT2 Receptors in Hyperthyroid Mice

Hyperthyroidism is characterized by an increased metabolic rate with the alteration of immune activity. The pineal hormone melatonin regulates various physiological activities through sensitization of MT1 and MT2 membrane receptors in mammals. In the present study we have evaluated the involvement of MT1 and MT2 receptors in melatonin mediated modulation of thyroid hormones and splenocyte proliferation in experimentally induced hyperthyroidic mice. The l-thyroxine treatment induced the hyperthyroidism in mice evidenced with hypersecretion of T3 and T4 hormones from thyroid gland. Hyperthyroidic state increased the TSH hormone level which might be inducing hyper activity in thyroid gland. Exogenous melatonin suppressed the thyroid hormones level as well as TSH level in circulation. The l-thyroxine treatment increased the splenocyte proliferation and showed synergic effects along with melatonin. l-thyroxine treated mice alone or along with melatonin treatment showed differential expression pattern of MT1 and MT2 receptors protein in thyroid and spleen tissues. It seems that melatonin regulates thyroid hormones and splenocyte proliferation through activation of MT1 and MT2 receptors.     

Role of thyroid hormones in human and laboratory animal reproductive health

The highly conserved nature of the thyroid gland and the thyroid system among mammalian species suggests it is critical to species survival. Studies show the thyroid system plays a critical role in the development of several organ systems, including the reproductive tract. Despite its highly conserved nature, the thyroid system can have widely different effects on reproduction and reproductive tract development in different species. The present review focuses on assessing the role of thyroid hormones in human reproduction and reproductive tract development and comparing it to the role of thyroid hormones in laboratory animal reproduction and reproductive tract development. The review also assesses the effects of thyroid dysfunction on reproductive tract development and function in humans and laboratory animals. Consideration of such information is important in designing, conducting, and interpreting studies to assess the potential effects of thyroid toxicants on reproduction and development.     

Hierarchies in the energy budget: Thyroid hormones and the evolution of human life history patterns

The evolution of human life history characteristics required dramatic shifts in energy allocation mechanisms compared with our primate ancestors. Thyroid hormones, such as thyroxine (T4) and triiodothyronine (T3), are sensitive to energy balance, and are significant determinants for both tissue-specific and whole-body metabolic rate. Thus, thyroid hormones are in part responsible for setting the body's overall energy budget and likely played an important role in the evolution of human life history patterns. We propose that the dynamics of mammalian T3 production, uptake, and action have evolved so that energy allocation prioritizes the high demands of brain development and functioning, often at the expense of growth and reproduction. This paper explores the role of thyroid hormone dynamics in the evolution of human encephalization, prolonged childhood and adolescence, long lifespans, reproduction, and human aging.     

Mechanisms and Consequences of Developmental Acceleration in Tadpoles Responding to Pond Drying

Many amphibian species exploit temporary or even ephemeral aquatic habitats for reproduction by maximising larval growth under benign conditions but accelerating development to rapidly undergo metamorphosis when at risk of desiccation from pond drying. Here we determine mechanisms enabling developmental acceleration in response to decreased water levels in western spadefoot toad tadpoles (Pelobates cultripes), a species with long larval periods and large size at metamorphosis but with a high degree of developmental plasticity. We found that P. cultripes tadpoles can shorten their larval period by an average of 30% in response to reduced water levels. We show that such developmental acceleration was achieved via increased endogenous levels of corticosterone and thyroid hormone, which act synergistically to achieve metamorphosis, and also by increased expression of the thyroid hormone receptor TRΒ, which increases tissue sensitivity and responsivity to thyroid hormone. However, developmental acceleration had morphological and physiological consequences. In addition to resulting in smaller juveniles with proportionately shorter limbs, tadpoles exposed to decreased water levels incurred oxidative stress, indicated by increased activity of the antioxidant enzymes catalase, superoxide dismutase, and gluthatione peroxidase. Such increases were apparently sufficient to neutralise the oxidative damage caused by presumed increased metabolic activity. Thus, developmental acceleration allows spadefoot toad tadpoles to evade drying ponds, but it comes at the expense of reduced size at metamorphosis and increased oxidative stress.     

哺乳动物季节性繁殖的内源年生物钟及光敏神经环路研究进展

生活在温带和寒带的哺乳动物在长期的进化过程中形成了季节性繁殖的生活史特征。哺乳动物的繁殖功能主要受到下丘脑-垂体-性腺轴(hypothalamic-pituitary-gonadal axis,HPGA)的调控。视交叉上核(suprachiasmatic nucleus,SCN)能够自发振荡并响应光周期信号的变化,引发褪黑素分泌的改变,并介导下游通路中下丘脑甲状腺激素、Kisspeptin和RF酰胺相关肽(RF amide-related peptide,RFRP)的节律性表达变化,从而调控哺乳动物的季节性繁殖。本文综述了哺乳动物季节性繁殖的内源年生物钟调控,并强调了光敏通路中包括甲状腺激素、Kisspeptin和RFRP在季节性繁殖调控中的重要作用。     

Endocrine mechanisms of seasonal adaptation in small mammals: from early results to present understanding

Seasonal adaptation is widespread among mammals of temperate and polar latitudes. The changes in physiology, morphology and behaviour are controlled by the photoneuroendocrine system that, as a first step, translates day lengths into a hormonal signal (melatonin). Decoding of the humoral melatonin signal, i.e. responses on the cellular level to slight alterations in signal duration, represents the prerequisite for appropriate timing of winter acclimatization in photoperiodic animals. Corresponding to the diversity of affected traits, several hormone systems are involved in the regulation downstream of the neural integration of photoperiodic time measurement. Results from recent studies provide new insights into seasonal control of reproduction and energy balance. Most intriguingly, the availability of thyroid hormone within hypothalamic key regions, which is a crucial determinant of seasonal transitions, appears to be regulated by hormone secretion from the pars tuberalis of the pituitary gland. This proposed neuroendocrine pathway contradicts the common view of the pituitary as a gland that acts downstream of the hypothalamus. In the present overview of (neuro)endocrine mechanisms underlying seasonal acclimatization, we are focusing on the dwarf hamster Phodopus sungorus (long-day breeder) that is known for large amplitudes in seasonal changes. However, important findings in other mammalian species such as Syrian hamsters and sheep (short-day breeder) are considered as well.     

甲壳动物高血糖激素家族生理功能研究进展

甲壳动物高血糖激素家族是甲壳动物特有的神经多肽激素家族,主要由眼柄的X-器窦腺复合体(XO-SG)合成与分泌,包括高血糖激素(CHH)、蜕皮抑制激素(MIH)、性腺抑制激素(GIH)和大颚器抑制激素(MOIH),协同调控着甲壳动物的生长、繁殖与蜕皮等生理生化过程.本文就目前CHH家族神经肽的功能研究,包括功能研究的方法、各个激素的功能以及分泌调控等研究进展作一综述.     

Evidence for a functional role of cholecystokinin receptors in the rat thyroid gland.

The aim of the present study was to examine the role of cholecystokinin (CCK) and/or cholecystokinin receptors subtypes (CCK1R and CCK2R) in the regulation of the thyroid gland structure and function. Animals were autopsied after 6 days of treatment with CCK or CCK receptor-specific antagonists (CCK1a--PD 140,548 or CCK2a--PD 135,158) solely or in combination with CCK. Results suggest that CCK exerts a stimulatory effect on follicular thyroid cells manifested by increased epithelium/colloid volume fraction ratio (E/C). Application of selective antagonists of CCK receptor subtypes has demonstrated that CCK acts through the CCK1 receptor subtype at the level of pituitary TSH. The model of endogenous hormone action reveals that thyroid CCK1 is responsible for the thyroid growth. It can be concluded that the physiological activity of CCK1 receptor plays a significant role in a complex interrelationship between TSH, vagal system and CCK1-dependent function of the thyroid gland.     

Structure of the thyroid gland, serum thyroid hormones, and the reproductive cycle of the Atlantic stingray, Dasyatis sabina.

This study examines the role of the thyroid gland in the control of reproduction in the viviparous Atlantic stingray, Dasyatis sabina. Thyroid activity in individuals in different reproductive stages was assessed both by microscopic examination of the gland, and by analysis of circulating levels of thyroid hormones from the same individuals. The thyroid gland is a cylindric organ, embedded in a connective tissue capsule, and composed of follicles, i.e., monolayer spheres of thyroid epithelial cells. Stingray follicular cells possess several characteristic features, namely apical cilia and a well-developed endoplasmic reticulum. Cells vary in size and shape, according to the activity of the gland. No structural differences were observed between the thyroid glands of the two sexes. Both thyroid hormones, triiodothyronine, [T(3)], and thyroxine, [T(4)], were detected in the serum of all animals examined. Levels ranged from 1.3-2.6 microg/100 ml for total T(4), and from 1.2-2.6 ng/ml for total T(3). The T(4) levels did not vary significantly in any group. Immature individuals and females undergoing oogenesis had the lowest levels of circulating T(3) and mature females from ovulation throughout gestation had high thyroid gland activity and high levels of circulating T(3). J. Exp. Zool. 284:505-516, 1999.     

Endocrine regulation of ovarian antral follicle development in cattle

Antral follicle growth in cattle occurs in two distinct phases; the first 'slow' growth phase spans the time from antrum acquisition to a size of approximately 3 mm detectable by transrectal ultrasound, and the second 'fast' phase is gondadotrophin-dependent and includes cohort growth, dominant follicle (DF) selection, and DF growth. This review summarises current concepts of the relative roles FSH and LH, ovarian and metabolic hormones play mainly in the second phase of antral follicle growth in animals of different reproductive and nutritional states. It is proposed that differential FSH response may enable one cohort follicle to become selected, and that follicular secretions, particularly inhibin, suppress FSH and thus are responsible for DF selection and dominance. Acute dependence of the DF on LH pulses will determine DF lifespan, and the LH pulse profile can be influenced by metabolic hormones such as leptin, providing one possible link for nutritional state and reproduction. Direct ovarian effects of acute and chronic changes in growth hormone, insulin and insulin-like growth factor (IGF)-I have been described on cohort follicles, DF oestrogen activity and on DF growth. Influences of metabolic hormones on early antral follicles undergoing their first 'slow' growth phase are less well described, yet metabolic hormones appear to enhance growth into the cohort available for FSH-induced emergence, and may influence subsequent developmental competence of oocytes.     

Effect of thyroid hormone and sex status on epidermal growth factor concentrations in the submandibular gland of a congenitally hypothyroid mouse model

Studies were performed to explore the role of thyroid hormone and sex status on epidermal growth factor concentrations in the submandibular gland of a congenitally hypothyroid mouse model designated hyt/hyt. The animals were studied at 20, 30 and 40 days of postnatal age. The euthyroid animals were homozygous or heterozygous for the hypothyroid gene. The homozygous euthyroid animals displayed a pattern of submandibular gland epidermal growth factor concentrations similar to those previously described in other mouse species and showed the expected sex differences. The hypothyroid animals had measurable but very low submandibular gland epidermal growth factor concentrations without sexual dimorphism. Serum thyroxine concentrations in the heterozygotes were comparable to those in the homozygous euthyroid animals, yet the animals had a delayed increase in epidermal growth factor concentrations combined with a later expression of female-male differences. The timing of the sex differences in submandibular gland epidermal growth factor concentrations followed a pattern similar to that seen for the timing of the first litter in these three genetically distinct groups. This infers the timing of the onset of puberty and suggests a role of androgens in the changes seen in epidermal growth factor concentrations. We conclude that thyroid hormone and sex status in this mouse model influence the pattern and concentrations of submandibular gland epidermal growth factor concentrations.     

Seasonal changes in vertebrate immune activity: mediation by physiological trade-offs

Animals living in temporally dynamic environments experience variation in resource availability, climate and threat of infection over the course of the year. Thus, to survive and reproduce successfully, these organisms must allocate resources among competing physiological systems in such a way as to maximize fitness in changing environments. Here, we review evidence supporting the hypothesis that physiological trade-offs, particularly those between the reproductive and immune systems, mediate part of the seasonal changes detected in the immune defences of many vertebrates. Abundant recent work has detected significant energetic and nutritional costs of immune defence. Sometimes these physiological costs are sufficiently large to affect fitness (e.g. reproductive output, growth or survival), indicating that selection for appropriate allocation strategies probably occurred in the past. Because hormones often orchestrate allocations among physiological systems, the endocrine mediators of seasonal changes in immune activity are discussed. Many hormones, including melatonin, glucocorticoids and androgens have extensive and consistent effects on the immune system, and they change in systematic fashions over the year. Finally, a modified framework within which to conduct future studies in ecological immunology is proposed, viz. a heightened appreciation of the complex but intelligible nature of the vertebrate immune system. Although other factors besides trade-offs undoubtedly influence seasonal variation in immune defence in animals, a growing literature supports a role for physiological trade-offs and the fitness consequences they sometimes produce.     

Effects of modifying olfactory and pineal gland function on the seasonality of semen production and plasma luteinizing hormone,testosterone and prolactin levels in rams

In an experiment designed to evaluate neuroendocrine mechanisms which could mediate seasonality of reproduction in Romney rams, the effects on semen production and plasma hormone levels of olfactory bulbectomy, cranial cervical ganglionectomy, or both operations, were studied over a period of 16 months.Concentrations and total numbers of spermatozoa in ejaculates from surgically treated rams were higher than in those from unoperated controls. Although mean fructose concentrations were lower in semen from treated animals, the pattern of seasonal changes in seminal fructose was similar in all groups of rams. Olfactory bulbectomy disrupted the regular seasonal changes in plasma luteinizing hormone (LH) levels, while cranial cervical ganglionectomy abolished the seasonality of secretion of both LH and prolactin. The annual pattern of testosterone secretion was not affected by any surgical treatment. Ganglionectomy reduced hydroxyindole-O-methyl transferase activity and cell volumes in pineal glands, so it was concluded that this treatment produced its effects by reducing the capacity of the pineal gland to respond to seasonal variations in daily photoperiod. No conclusions could be drawn about the role of olfactory function in regulating seasonality of reproduction in rams.     

The role of oxidative stress in physiological and pathological processes in the thyroid gland; possible involvement in pineal-thyroid interactions

Reactive oxygen species (ROS) play an important role in physiological processes, but - when being in excess - ROS cause oxidative damage to molecules. Under physiological conditions, the production and detoxification of ROS are more-or-less balanced. Also in the thyroid, ROS and free radicals participate in physiological and pathological processes in the gland. For example, hydrogen peroxide (H2O2) is crucial for thyroid hormone biosynthesis, acting at different steps of the process. Additionally, H2O2 is believed to participate in the Wolff-Chaikoff's effect, undergoing in conditions of iodide excess in the thyroid. Much evidence has been accumulated indicating that oxidative stress is involved in pathomechanism of thyroid disease, e.g., Graves' disease, goiter formation or thyroid cancer. Melatonin (N-acetyl-5-methoxytryptamine) - the main secretory product of the pineal gland - is a well-known antioxidant and free radical scavenger, widely distributed in the organism. Mutual relationships between the pineal gland and the thyroid have - for a long time - been a subject of intensive research. The abundant to-date's evidence relates mostly to the inhibitory action of melatonin on the thyroid growth and function and - to a lesser extent - to the stimulatory effects of thyroid hormones on the pineal gland. It is highly probable that under physiological conditions melatonin and, possibly, other antioxidants regulate ROS generation for thyroid hormone synthesis. We believe that melatonin may protect against extensive oxidative damage in the course of certain thyroid disorders or in case of a harmful action of some external factors on the thyroid. Thus, oxidative damage and the protective action of antioxidants, melatonin included, may occur during both physiological and pathological processes in the thyroid, however, this assumption, requires further studies.     

Effect of thyroid hormone administration on estrogen-induced sex behavior in female mice

Effects of thyroid hormones on reproductive processes have been described in sheep, birds, and rats. To extend this subject to mice for eventual analysis with genetically modified animals, we looked for effects of thyroid hormone treatment on lordosis behavior of ovariectomized estrogen-treated female mice. High doses of thyroid hormones reduced lordosis behavior. Since we could not explain this result by pharmacokinetic or peripheral effects, we infer that it worked by a central mechanism. Future investigations must determine whether endogenous fluctuations within the thyroid's normal physiological range have any behavioral effects.     

Effects of Triiodothyronine (T3) Supplementation Upon Ozone-Induced Lung Injury

Ozone exposure results in an acute decrease in the serum levels of thyroid hormones; the physiologic sequelae of this are unclear. Whereas thyroid hormone supplementation appears to benefit pulmonary function in septic, oxyradical models of injury, thyroid hormone increases ozone toxicity. We demonstrated an increase in metabolic rate and pulmonary injury in lungs from ozone exposed, T₃ treated animals. This was evidenced by an increase in pulmonary weight gain, vascular perfusion pressure, and decrease in compliance in the supplemented animals. However, an increase in alkane generation, as an index of lipid peroxidation, was not seen in the ozone exposed, hormonally treated animals. This suggests that although thyroid hormone supplementation increases metabolic rate and ozone toxicity, an increased rate of lipid peroxidation plays a minimal role.