Stress and the development of agonistic behavior in golden hamsters

Aggressive behavior can be studied as either offensive or defensive responses to a stimulus. The studies discussed in this review are focused on the peripubertal development of offensive aggression in male golden hamsters and its responsiveness to repeated social stress. Quantitative and qualitative changes in offensive responses were analyzed during this period. Quantitative changes in offensive responses were observed as decreased frequency of attacks. Qualitative changes were observed as changes in attack types, as animals reorient their attacks gradually from the face to the lower belly and rump. These developmental changes were altered by repeated exposure to social stress during early puberty. Daily exposure to aggressive adults during early puberty accelerated the qualitative development of offensive responses and the onset of adult-like offensive responses. In contrast, social stress had little effect on the quantitative changes associated with early puberty. However, social stress was associated with higher attack frequency during adulthood. These effects of stress during early puberty contrast with those observed with animals in late puberty. At that time, repeated exposure to aggressive adults inhibits offensive aggression. These data constitute the basis for a new theory on the development of agonistic behavior that includes the following hypotheses. First, it is hypothesized that mid-puberty is marked by a change in responsiveness to repeated social stress. As such, differences in stress responsiveness from social interactions are interpreted as a basic distinction between play fighting and adult aggression. Second, it is also hypothesized that a common neural circuitry mediates the activation of offensive responses during play fighting and adult aggressive interactions.     

Changes in circadian rhythms during puberty in Rattus norvegicus: developmental time course and gonadal dependency

During puberty, humans develop a later chronotype, exhibiting a phase-delayed daily rest/activity rhythm. The purpose of this study was to determine: 1) whether similar changes in chronotype occur during puberty in a laboratory rodent species, 2) whether these changes are due to pubertal hormones affecting the circadian timekeeping system. We tracked the phasing and distribution of wheel-running activity rhythms during post-weaning development in rats that were gonadectomized before puberty or left intact. We found that intact peripubertal rats had activity rhythms that were phase-delayed relative to adults. Young rats also exhibited a bimodal nocturnal activity distribution. As puberty progressed, bimodality diminished and late-night activity phase-advanced until it consolidated with early-night activity. By late puberty, intact rats showed a strong, unimodal rhythm that peaked at the beginning of the night. These pubertal changes in circadian phase were more pronounced in males than females. Increases in gonadal hormones during puberty partially accounted for these changes, as rats that were gonadectomized before puberty demonstrated smaller phase changes than intact rats and maintained ultradian rhythms into adulthood. We investigated the role of photic entrainment by comparing circadian development under constant and entrained conditions. We found that the period (τ) of free-running rhythms developed sex differences during puberty. These changes in τ did not account for pubertal changes in entrained circadian phase, as the consolidation of activity at the beginning of the subjective night persisted under constant conditions in both sexes. We conclude that the circadian system continues to develop in a hormone-sensitive manner during puberty.     

Growth disorders in children with type 1 diabetes mellitus

The aim of the research was to analyze anthropometric variables in children with type 1 diabetes mellitus (DM) in relation with the stage of pubertal development at onset of disease and quality of metabolic control over five-year long observation. Diagnosed children were taller than their peers. This especially referred to age group between 4 and 9.5 years. On the whole, weight of the patients and healthy controls did not differ. However, the diagnosed children had substantially lower weight in puberty than healthy controls. Body mass index was significantly lower in the group of diagnosed children on the whole and in puberty. During a five-year long observation patients have had a significant retardation of growth. However, that retardation referred primarily to patients in prepuberty. Growth retardation was more pronounced with bad metabolic control. Growth was satisfactory if onset of disease had been in puberty. A significant weight gain was observed in patients in puberty whereas in those in prepuberty there was no significant change of body weight at the end of five-year long observation. Metabolic control did not affect observed changes. There were significant differences of anthropometric variables between those suffering from type 1 DM and their peers. The differences depended on the age at onset. The disease had a negative effect on growth with onset in prepuberty, whereas in puberty growth was satisfactory. However, puberty was a period in which patients increased their weight excessively. Prepuberty was a period in which growth had been significantly affected by metabolic control.     

Interaction between isolation rearing and social development on exploratory behavior in male rats

The effect of isolation on exploratory behavior has been shown to differ depending on the developmental stages of male rats. However, there has been little systematic comparison of the frequencies and the patterns of exploratory behavior across the developmental stages. The present study assessed the frequencies of exploration using the emergence test and exploratory patterns in the open-field test in three developmental stages of male rats: juvenile, post-puberty, and adult. A lower propensity for exploration was observed in rats isolated during the juvenile stage, as assessed by increased latency and decreased duration of exploratory behaviors compared to pair-reared rats, and this tendency was maintained in adulthood. Altered patterns of exploratory behavior were demonstrated both in rats isolated in adulthood, who showed an increased active pattern, and those pair-reared following puberty, who shifted to a more passive pattern. However, rats isolated during the juvenile stage did not change their exploratory patterns following puberty. These results suggest that the changes in the exploratory pattern, which can be observed in adulthood, are associated with the emergence of adult-like dominance relationships. Juvenile-isolated rats did not show these changes following puberty, suggesting the importance of social interaction as juveniles for the ontogenetic emergence of behavioral flexibility implicated in the regulation of exploratory patterns.     

Studying adaptive changes in the behaviour of infected hosts: a long and winding road

The effect of isolation on exploratory behavior has been shown to differ depending on the developmental stages of male rats. However, there has been little systematic comparison of the frequencies and the patterns of exploratory behavior across the developmental stages. The present study assessed the frequencies of exploration using the emergence test and exploratory patterns in the open-field test in three developmental stages of male rats: juvenile, post-puberty, and adult. A lower propensity for exploration was observed in rats isolated during the juvenile stage, as assessed by increased latency and decreased duration of exploratory behaviors compared to pair-reared rats, and this tendency was maintained in adulthood. Altered patterns of exploratory behavior were demonstrated both in rats isolated in adulthood, who showed an increased active pattern, and those pair-reared following puberty, who shifted to a more passive pattern. However, rats isolated during the juvenile stage did not change their exploratory patterns following puberty. These results suggest that the changes in the exploratory pattern, which can be observed in adulthood, are associated with the emergence of adult-like dominance relationships. Juvenile-isolated rats did not show these changes following puberty, suggesting the importance of social interaction as juveniles for the ontogenetic emergence of behavioral flexibility implicated in the regulation of exploratory patterns.     

Puberty in the male owl monkey (Aotus trivirgatus griseimembra): A study of physical and hormonal development

In the male owl monkey (Aotus trivirgatus),the onset of puberty occurs at between 211 and 337 days (median, 313) as indicated by longitudinal measurements of plasma testosterone in six subjects. Larger rises in plasma testosterone were observed between 300 and 400 days. Pubertal increases in body weight and testicular volume are not pronounced in this species. Young animals first entered the weight range for adult males (800–1080 g) when they were between 370 and 520 days of age (median, 472). Marked growth of the subcaudal scentmarking gland occurred during puberty. The first signs of development of this gland (stiffening and discoloration of overlying hairs) were noted between 282 and 370 days (median 316), and it had attained an adult structure by 336–442 days (median, 397). These changes were androgen dependent as indicated by the fact that treatment of a prepubertal male with testosterone stimulated the subcaudal gland to develop prematurely. Hormonal and physical changes during puberty were the same whether males remained with their parents or were caged alone. There was no indication that puberty was retarded in males which had remained in their natal groups.     

Time-related neuroendocrine manifestations of puberty: a combined clinical and experimental approach extracted from the 4th Belgian Endocrine Society lecture

The neuroendocrine manifestations of puberty converge on changes in GnRH secretion. Their appraisal through the assay of GnRH-like material in 24-hour urine extracts shows an increased excretion of this material in the late prepubertal period. The most striking pubertal changes in GnRH secretion occur on a circadian and ultradian basis. In man, they can be evaluated only indirectly. The circadian variations in LH and FSH secretion characteristic of puberty may be observed in timed fractions of 24-hour urine with some delay when compared to the variations of plasma levels. Studies on the frequency of pulsatile LH secretion and during chronic intermittent administration of GnRH support the existence of an increased frequency of GnRH secretory episodes at puberty. LH response to synthetic GnRH is directly related to the frequency of stimulation by endogenous GnRH pulses and provides a very useful index of neuroendocrine maturation in patients with delayed or precocious puberty. A direct evaluation of pulsatile GnRH secretion is possible using the rat hypothalamus in vitro. In these experimental conditions, the frequency of pulsatile GnRH release increases during very early stages of sexual maturation in the male rat. GnRH itself and beta-endorphin are inhibitory regulators of GnRH secretion in vitro and may participate in the mechanisms restraining the pulse-generating machinery in the hypothalamus before puberty.     

Advancement of puberty in ewe lambs by active immunisation against inhibin early in life

Active immunisation of lambs early in life with inhibin can advance puberty and increase ovulation rate but these effects appear not to be mediated through changes in FSH concentrations. The aims of this study were to advance puberty in ewe lambs and determine if increased plasma concentrations of gonadotropins are responsible for the advancement of puberty. Ewe lambs were immunised at 3, 7 and 15 weeks of age against either a synthetic inhibin alpha subunit peptide 1–32 conjugated to human serum albumin (HSA), or an inhibin preparation purified from porcine follicular fluid (porcine monoclonal purified inhibin; pMPI), or HSA alone (control immunogen).Immunisation with inhibin alpha peptide 1–32 produced antibodies which bound iodinated native bovine inhibin and advanced puberty (time of first ovulation) and increased ovulation rate but did not significantly increase plasma FSH concentrations, although LH concentrations were lower (P < 0.01) on a number of occasions. In contrast, immunisation with pMPI significantly (P < 0.01) increased FSH and LH concentrations following the first booster immunisation, although FSH was only transiently elevated. Despite these increases in gonadotropins, no advancement of puberty was observed in PMPI immunised ewe lambs.This study confirms that active immunisation of ewe lambs early in life against inhibin advances puberty via a mechanism which does not significantly increase plasma gonadotrophin concentrations. Immunisation to advance puberty also results in persistent increases in ovulation rates in later breeding seasons.     

A study of seasonally delayed puberty in the male hare, Lepus Europaeus.

The brown hare, Lepus europaeus, has a mating season which extends from January to September. Adult males exhibit pronounced seasonal changes in the reproductive tract which are associated with changes in LH secretion. Maximum plasma levels of immunoreactive LH occur between March and June and minimal levels in the autumn non-mating period from September to December; this seasonal cycle in gonadotrophin output is reflected by the appropriate changes in the secretion of testosterone from the testes and in the activity of the accessory sex glands. Juvenile animals reach puberty only during the adult mating season, and the age of puberty thus varies with the date of birth. Males born before May reach puberty and become fertile at 3 months of age, while those born from May to July grow to a mature body size during the autumn non-mating season but puberty is delayed for several months. Since some animals experiencing delayed puberty were found to have elevated plasma levels of LH and testosterone, it is concluded that puberty is not completely suppresed by the environmental effects of the autumn, but that the developmental process is prolonged, resulting in the juveniles being synchronized with the adults in their reproductive activity.     

Forty years trends in timing of pubertal growth spurt in 157,000 Danish school children

Background

Entering puberty is an important milestone in reproductive life and secular changes in the timing of puberty may be an important indicator of the general reproductive health in a population. Too early puberty is associated with several psychosocial and health problems. The aim of our study was to determine if the age at onset of pubertal growth spurt (OGS) and at peak height velocity (PHV) during puberty show secular trends during four decades in a large cohort of school children.

Methods and Findings

Annual measurements of height were available in all children born from 1930 to 1969 who attended primary school in the Copenhagen Municipality. 135,223 girls and 21,612 boys fulfilled the criteria for determining age at OGS and age at PHV. These physiological events were used as markers of pubertal development in our computerized method in order to evaluate any secular trends in pubertal maturation during the study period (year of birth 1930 to 1969). In this period, age at OGS declined statistically significantly by 0.2 and 0.4 years in girls and boys, respectively, whereas age at PHV declined statistically significantly by 0.5 and 0.3 years in girls and boys, respectively. The decline was non-linear with a levelling off in the children born between 1940 and 1955. The duration of puberty, as defined by the difference between age at OGS and age at PHV, increased slightly in boys, whereas it decreased in girls.

Conclusion

Our finding of declining age at OGS and at PHV indicates a secular trend towards earlier sexual maturation of Danish children born between 1930 and 1969. Only minor changes were observed in duration of puberty assessed by the difference in ages at OGS and PHV.     

Genomic and transcriptomic analyses reveal selection of genes for puberty in Bama Xiang pigs

The Bama Xiang pig(BMX) is a famous early-maturing Chinese indigenous breed with a two-end black coat.To uncover the genetic basis of the BMX phenotype,we conducted comparative genomic analyses between BMX and East Asian wild boars and Laiwu pigs,respectively. Genes under positive selection were enriched in pathways associated with gonadal hormone and melanin synthesis, consistent with the phenotypic changes observed during development in BMX pigs. We also performed differentially expressed gene analysis based on RNA-seq data from pituitary tissues of BMX and Large White pigs. The CTTNBP2 NL, FRS2,KANK4, and KATNAL1 genes were under selection and exhibited expressional changes in the pituitary tissue, which may affect BMX pig puberty. Our study demonstrated the positive selection of early maturity in the development of BMX pigs and advances our knowledge on the role of regulatory elements in puberty evolution in pigs.     

Preweaning over- and underfeeding alters onset of puberty in the rat without affecting kisspeptin

The perinatal nutritional environment can permanently influence body weight, potentially leading to changes in puberty onset and reproductive function. We hypothesized that perinatal under- or overfeeding would alter puberty onset and influence concentrations of a neuropeptide crucial for successful puberty, kisspeptin. We manipulated Wistar rat litter sizes to derive small (SL), control (CL), and large (LL) litters containing 4, 12, and 20 rat pups respectively. This manipulation results in an overweight phenotype in SL rats and a lean phenotype in LL that persists throughout life. To investigate whether successful puberty onset is affected by neonatal under- or overfeeding, we examined indices of growth and development, including the onset of puberty, as well as the central expression of Kiss1 mRNA in these pups. Male LL rats reached puberty later than those from CL. These males also had reduced plasma testosterone and elevated 17beta-estradiol concentrations at puberty. The age at puberty onset was not affected in SL males despite accelerated growth. In females, puberty onset was not significantly delayed by having a lean phenotype, and steroid hormones were not affected. The age at onset was, however, younger in the SL females. Kiss1 mRNA in the hypothalamus was not affected by neonatal nutrition either at puberty or 7 days later. Our findings show early life underfeeding in males and overfeeding in females significantly affects puberty onset, altering steroid hormone concentrations in males, but this is not related to changes in hypothalamic kisspeptin.     

Pituitary response to LHRH, LH pulsatility and plasma melatonin and prolactin changes in ewe lambs treated with melatonin implants to delay puberty

Prepubertal ewe lambs were treated with empty or filled melatonin implants. The implants were placed s.c. at birth and pituitary responsiveness to various doses of LHRH, LH/FSH pulsatility and prolactin and melatonin secretion were examined at 10, 19, 28, 36 and 45 weeks of age. Control animals (N = 10) showed no consistent alteration in pituitary responsiveness to LHRH during development. Ewes treated with melatonin (N = 10) had puberty onset delayed by 4 weeks (P less than 0.03) but no effect of melatonin on LH or FSH response to LHRH injection was observed at any stage of development. In the control and melatonin-treated ewe lambs the responses to LHRH injection were lower during darkness than during the day at all stages of development. No consistent differences in LH or FSH pulsatility were observed between treatment groups or during development. Prolactin concentrations, however, failed to decrease at the time of puberty (autumn) in the melatonin-treated group. Melatonin-treated ewe lambs maintained normal rhythmic melatonin production which was superimposed on a higher basal concentration and showed the same increase in melatonin output with age as the control ewes. These results indicate that the delayed puberty caused by melatonin implants is not due to decreased pituitary responsiveness to LHRH or to dramatic changes in basal LH or FSH secretion.     

Influence of cognitive load on the body functional state in children aged 9 to 12 years during early stages of puberty

This article analyzes heart rate variability (HRV), the glucocorticoid function of adrenal glands, and brain electrical activity (EA) in children aged 9 to 12 years to study their functional state during early stages of puberty. The cognitive load (mental arithmetic) caused low-frequency waves in the heart rate spectrum in all subjects, regardless of the puberty stage and gender. With respect to the age range under study, the hormonal response to the arithmetic test, expressed in a decrease in the level of cortisol, was observed in boys only at the third stage of puberty. The visual analysis of the background electrical encephalogram showed frequent generalized bilateral and synchronous changes in the electrical activity (EA) in the form of diencephalic signs in children. The features of the relationship between the autonomic nervous system and the hypothalamic pituitary-adrenal system have been revealed in children aged 9 to 12 years during cognitive load. The closest correlations between HRV indices and cortisol levels have been found in girls at the first stage and boys at the third stage of puberty.     

Embryo production by ovum pick up in unstimulated calves before and after puberty

The possibility of producing embryos from oocytes repeatedly collected from unstimulated calves was tested, and results obtained before and after puberty were compared in the same animals. Ovum pick-up (OPU) coupled with in vitro embryo production was used on 2 sets of 7 and 9 calves, aged 7 to 10 m.o. at the start of the experiment. The oocytes were collected twice a week during a 2-m.o. period before puberty and a 1-m.o. period after puberty. Oocytes were fertilized and co-cultured with cumulus cells in modified synthetic oviduct fluid (SOF) up to Day 7 post insemination. Some Day 7 blastocysts were vitrified and transferred to recipient heifers. An average of 3.8 to 6.8 follicles was punctured per OPU session; 1.9 to 3.1 oocytes were collected, of which more than 60% were of good quality. The number of punctured follicles and collected oocytes varied between donors. Blastocyst rates of 19 to 27% were obtained for the 2 sets. Three normal calves were born from the transfer of 20 vitrified embryos. While no significant difference was observed for the first set of calves, a significant decrease in the number of punctured follicles was observed after puberty in the second set. A direct correlation was also obtained between the number of follicles punctured before and after puberty in the same animal. In conclusion, oocytes can be collected by repeated OPU in calves 7 to 10 m.o. old without affecting their growth or the onset of puberty. An average of 5 to 11 (range 0 to 16) blastocysts per donor was produced over 2 month. However, important variations were found between donors. The correlation observed for the number of follicles punctured before and after puberty suggests that this parameter is determined before puberty.     

Endocrine mechanisms of puberty in heifers. Role of hypothalamo-pituitary estradiol receptors in the negative feedback of estradiol on luteinizing hormone secretion

The hypothesis tested was that the decline in negative feedback of estradiol on secretion of luteinizing hormone (LH) that occurs as puberty approaches in heifers results from a decline in the number of receptors for estradiol in the hypothalamus and/or pituitary. In addition, associated changes in receptors for luteinizing hormone-releasing hormone (LHRH) in the pituitary, ovarian follicle development, and uterine growth were characterized. Fifty prepubertal heifers, 234 to 264 days of age, were used. Six heifers of median body weight were designated controls, and sequential blood samples were collected at 20-min intervals for 24 h every 2 wk from 249 days of age through puberty and analyzed for concentrations of LH. Frequency of LH pulses/24 h was regressed on number of days prepuberty to develop a prediction equation for puberty. Thirty of the remaining 44 heifers were killed at 253, 302, and 351 days of age (n = 10/group), and tissues for described analyses were collected. Three to 5 days before tissue collection, sequential blood samples were obtained from these heifers, as described for control heifers to determine frequency of release of LH. With this information, number of days prepuberty at the time of tissue collection was estimated from the prediction equation developed with data from control heifers. The average age at puberty in control heifers was 366 days. The average age at puberty of heifers that were not killed or included in the control group (n = 14) was 360 days. Receptor and morphological data were related to the estimated onset of puberty. Cytosolic concentration of receptors for estradiol (fmoles receptor/mg cytosolic protein) in the anterior hypothalamus, medial basal hypothalamus, and anterior pituitary declined (p less than 0.05) as puberty approached. No change in concentration of receptors for estradiol was observed in the stalk median eminence or preoptic area. The concentration of receptors for LHRH in the anterior pituitary did not change as puberty approached. Uterine weight increased rapidly during the 50 days preceding puberty. The number of small, medium, or large follicles and the wet, pressed, or dry weight of the ovaries did not change as puberty approached. Follicles with a diameter greater than 12 mm were found only in the 3 heifers estimated to be closest to puberty at the time of tissue collection. The hypothesis that the decline in estradiol feedback on secretion of LH during the prepubertal period in heifers may result from a decline in the concentration of binding sites for estradiol at the hypothalamus and/or pituitary is supported by this study.     

Reactivity to estradiol of thymic cells from female mice before and after puberty.

The reactivity to estradiol of thymic cells from female mice representing different stages of sexual maturation was investigated. It was found that estradiol administered in pharmacological doses can evoke in thymuses of ovariectomized mice changes imitating those observed during puberty with the reactivity to estradiol changing along with the process of sexual maturation. It is most likely that the changes of reactivity are due to extragonadal factors.     

Pubertal maturation modifies the regulation of insulin-like growth factor-I receptor signaling by estradiol in the rat prefrontal cortex

The transition from adolescence to adulthood is accompanied by substantial plastic modifications in the cerebral cortex, including changes in the growth and retraction of neuronal processes and in the rate of synaptic formation and neuronal loss. Some of these plastic changes are prevented in female rats by prepubertal ovariectomy. The ovarian hormone estradiol modulates neuronal differentiation and survival and these effects are in part mediated by the interaction with insulin-like growth factor-I (IGF-I). In this study, we have explored whether the activation by estradiol of some components of IGF-I receptor signaling is altered in the prefrontal cortex during puberty. Estradiol administration to rats ovariectomized after puberty resulted, 24 h after the hormonal administration, in a sustained phosphorylation of Akt and glycogen synthase kinase 3 beta in the prefrontal cortex. However, this hormonal effect was not observed in animals ovariectomized before puberty. These findings suggest that during pubertal maturation there is a programming by ovarian hormones of the future regulatory actions of estradiol on IGF-I receptor signaling in the prefrontal cortex. The modification in the regulation of IGF-I receptor signaling by estradiol during pubertal maturation may have implications for the developmental changes occurring in the prefrontal cortex in the transition from adolescence to adulthood.     

Mast cells in the human testis and epididymis from birth to adulthood

Mast cells are a constant cell-type in the connective tissues of the human testis and epididymis from birth to adulthood. Ultrastructural study shows that these cells are similar to those found in other connective tissues. Histometric studies revealed that the number of mast cells in the interstitium, mediastinum and albuginea of the testis as well as in the epididymal connective tissue increases slightly during infancy, decreases during childhood, and then increases again at puberty. Increases at puberty are particularly evident in both the testicular interstitium and the epididymis. During adulthood, the number of mast cells progressively decreases in all testicular and epididymal connective tissues. Changes in mast cell number may be related to changes observed in the development of testicular connective tissue which occurs primarily during infancy and puberty.     

Chronotype changes during puberty depend on gonadal hormones in the slow-developing rodent, Octodon degus

During puberty, human adolescents develop a later chronotype, exhibiting a delay in the timing of rest and activity as well as other daily physiological rhythms. The purpose of this study was to determine whether similar changes in chronotype occur during puberty in a laboratory rodent species, and, if so, to determine whether they are due to pubertal hormones acting on the circadian timekeeping system. To test this hypothesis, we carefully tracked daily activity rhythms across puberty in the slow-developing rodent Octodon degus. We confirmed that male degus showed a large reorganization of activity rhythms that correlated with secondary sex development during puberty, including a loss of bimodality and a 3-5 h phase-advance. Similar to humans, this circadian reorganization showed distinct sex differences, with females showing little change during puberty in two separate experiments. Prepubertal gonadectomy (GDX) eliminated the changes, whereas SHAM gonadectomy had little impact. Therefore, gonadal hormones are likely to play a role in pubertal changes in chronotype in this rodent species. Using evidence from a variety of species, including our recent studies in the rat, we conclude that chronotype changes during puberty are a well-demonstrated phenomenon in mammals.