Anovulation in non-reproductive female Damaraland mole-rats (Cryptomys damarensis)

Within colonies of Damaraland mole-rats (Cryptomys damarensis), anovulation in non-reproductive females is thought to play an important role in maintaining reproductive skew. Pituitary sensitivity and ovarian structure were examined in three groups of females that differed with respect to their social environment and breeding status to determine whether anovulation is due to inhibitory social cues or is merely the result of a lack of copulatory stimulation. The contribution of gonadal steroid negative feedback to neuroendocrine differences in the reproductive systems of the respective groups was also investigated. LH secretion after a 0.5 micrograms GnRH challenge in females that had been removed from the presence of the breeding individuals for at least 6 months (removed non-reproductive females) was significantly higher than in non-reproductive females in the colony, but significantly lower than in reproductive females. In both removed non-reproductive females and reproductive females, corpora lutea were observed in ovaries of seven of eight females, indicating that ovulation occurs spontaneously in subordinate females on removal from the breeding pair. Circulating progesterone concentrations in removed non-reproductive females were significantly higher than in non-reproductive females, indicating that circulating progesterone is not responsible for infertility in non-reproductive females. Indeed, after hystero-ovariectomy, reproductive females continued to show significantly greater GnRH-stimulated LH secretion than non-reproductive females. Thus, differential inhibition of gonadotrophin secretion in breeding and non-breeding females occurs independently of gonadal steroids. It is concluded that female Damaraland mole-rats are spontaneous ovulators and that anovulation results from inhibitory social cues within the colony, not a lack of copulatory stimulation. Since non-reproductive females are infertile, inhibition of the hypothalamo-pituitary-gonadal axis has the potential to play a causal role in maintaining reproductive skew in colonies of C. damarensis.     

Are non-reproductive male highveld mole-rats, Cryptomys hottentotus pretoriae physiologically suppressed while in the confines of the natal colony?

The highveld mole-rat, Cryptomys hottentous pretoriae is a social, subterranean, co-operative breeder with a high reproductive skew. The relationship between reproductive status and reproductive physiology in male highveld mole-rats was investigated. Testicular morphometrics, histological parameters, plasma testosterone concentrations and sperm motility parameters were studied in 31 males (14 reproductive and 17 non-reproductive males). Reproductive males were significantly larger than non-reproductive males, with testicular mass and volume corrected for body mass considerably larger for the reproductive males. Circulating plasma testosterone concentrations of reproductive males were not significantly higher than non-reproductive males (reproductive males 10.3±1.8 nmol l⁻¹ vs non-reproductive males 7.3±1.74 nmol l⁻¹). Sperm motility parameters were measured, but no significant differences were found between reproductive and non-reproductive males. All 14 reproductive males had motile sperm, whereas 13 of the 17 (76%) of non-reproductive males possessed motile sperm. A typical ejaculate of a reproductive male contains 48.3% motile sperm characterized by a high percentage of flagellar defects, whereas the non-reproductive male has an ejaculate containing 45.6% motile sperm with a high percentage of head defects. It is apparent that non-reproductive males are not physiologically suppressed from reproducing. Moreover, the non-reproductive males are excluded from incestuous matings as a result of being the offspring of the reproductive female.     

LH responses to single doses of exogenous GnRH by social Mashona mole-rats: a continuum of socially induced infertility in the family Bathyergidae.

The Mashona mole-rat, Cryptomys darlingi, exhibits an extreme reproductive division of labour. Reproduction in the colony is restricted to a single breeding pair. The non-reproductive male and female colony members are restrained from sexual activity by being familiar and related to one another and the reproductive animals. Circulating basal concentrations of luteinizing hormone (LH) as well as LH levels measured in response to a single exogenous gonadotropin releasing hormone (GnRH) challenge are not significantly different between the reproductive and non-reproductive groups of either sex. Socially induced infertility in both non-reproductive males and females does not result from a reduced pituitary secretion of LH or decreased sensitivity to hypothalamic GnRH, but rather appears to result from an inhibition of reproductive behaviour in these obligate outbreeders. The African mole-rats exhibit a continuum of socially induced infertility with differing social species inhabiting regions of varying degrees of aridity. In this continuum a transition from a predominantly behavioural repression in a social mesic-adapted species through to complete physiological suppression lacking incest avoidance in an arid-adapted eusocial species occurs in this endemic African family of rodents.     

Hormonally derived sex pheromones in fish: exogenous cues and signals from gonad to brain

Living in a medium that can limit visual information but readily exposes the olfactory organ to hormonal compounds released by conspecifics, fish throughout their long evolutionary history have had both clear cause and ample opportunity to evolve olfactory responsiveness to these potentially important chemical cues (hormonal pheromones). Indeed, water-borne steroids, prostaglandins, and their metabolites are detected with great sensitivity and specificity by the olfactory organs of diverse fishes, and exert important effects on reproductive behavior and physiology in major taxa including carps (goldfish), catfishes, salmon, and gobies. Best understood are goldfish, where periovulatory females sequentially release a preovulatory steroid pheromone and a postovulatory prostaglandin pheromone that dramatically affect male behavior, physiology, and reproductive fitness. Although the diverse array of hormonal products released and detected by fish indicates clear potential for species-specific hormonal pheromones, olfactory recordings showing similar patterns of hormone detection among closely related species provide little evidence of selection for specificity. By demonstrating that the actions of sex hormones and related products are not limited to reproductive synchrony within the individual, the relatively recent discovery of hormonal pheromones has considerably expanded our understanding of fish reproductive function, while providing valuable model systems for future study of olfactory function and pheromone evolution.     

Exploring the mechanisms regulating regeneration of deer antlers

Deer antlers are the only mammalian appendages capable of repeated rounds of regeneration; every year they are shed and regrow from a blastema into large branched structures of cartilage and bone that are used for fighting and display. Longitudinal growth is by a process of modified endochondral ossification and in some species this can exceed 2 cm per day, representing the fastest rate of organ growth in the animal kingdom. However, despite their value as a unique model of mammalian regeneration the underlying mechanisms remain poorly understood. We review what is currently known about the local and systemic regulation of antler regeneration and some of the many unsolved questions of antler physiology are discussed. Molecules that we have identified as having potentially important local roles in antlers include parathyroid hormone-related peptide and retinoic acid (RA). Both are present in the blastema and in the rapidly growing antler where they regulate the differentiation of chondrocytes, osteoblasts and osteoclasts in vitro. Recent studies have shown that blockade of RA signalling can alter cellular differentiation in the blastema in vivo. The trigger that regulates the expression of these local signals is likely to be changing levels of sex steroids because the process of antler regeneration is linked to the reproductive cycle. The natural assumption has been that the most important hormone is testosterone, however, at a cellular level oestrogen may be a more significant regulator. Our data suggest that exogenous oestrogen acts as a 'brake', inhibiting the proliferation of progenitor cells in the antler tip while stimulating their differentiation, thus inhibiting continued growth. Deciphering the mechanism(s) by which sex steroids regulate cell-cycle progression and cellular differentiation in antlers may help to address why regeneration is limited in other mammalian tissues.     

Different patterns of metabolism determine the relative anabolic activity of 19-norandrogens

Testosterone, the principal androgen secreted by Leydig cells, exerts a wide range of actions including growth of the male reproductive tract (androgenic effects) and growth of non-reproductive tissues such as muscle, kidney, liver, and salivary gland (anabolic effects). As androgenic steroids were discovered some were found to have relatively more anabolic than androgenic activity. The results reviewed in this report suggest that these differences result, in part, from the differential metabolism of the steroids in individual tissues and the varied activities of the individual metabolites. In the accessory sex organs (e.g. the prostate) testosterone is 5-reduced to dihydrotestosterone (DHT) which, due to its higher affinity for androgen receptors (AR), amplifies the action of testosterone. In contrast, when 19-nortestosterone (NT) is 5-reduced, its affinity for AR decreases, resulting in a decrease in its androgenic potency. However, their anabolic potency remains unchanged since significant 5-reduction of the steroids does not occur in the muscle. 7-methyl-19-nortestosterone (MENT) does not get 5-reduced due to steric hindrance from the 7-methyl group. Therefore, the androgenic potency of MENT is not amplified as happens with testosterone. These metabolic differences are responsible for the increased anabolic activity of NT and MENT compared to testosterone. Part of the biological effects of testosterone are mediated by its aromatization to estrogens. The fact that MENT is also aromatized to 7-methyl estradiol, a potent estrogen, in vitro by human placental and rat ovarian aromatase suggests that some of the anabolic actions of MENT may be mediated by this estrogen.     

The male red-sided garter snake (Thamnophis sirtalis parietalis): reproductive pattern and behavior

Among the small group of species (e.g., some temperate zone turtles, snakes, and bats) that exhibit a dissociated reproductive pattern, the red-sided garter snake (Thamnophis sirtalis parietalis) is probably the most well studied. For these species, courtship and mating occur immediately upon emergence from winter dormancy; the gonads remain essentially inactive. Male red-sided garter snakes are a particularly informative animal model for examining the role of neuroendocrine factors associated with reproductive physiology and behavior because unlike species that exhibit an associated reproductive pattern, in which sex steroids initiate and control sexual behavior, reproductive behavior in the male garter snake appears to be independent of circulating sex hormone control. In fact, the only factor associated with the initiation of courtship behavior and mating in the male garter snake is an extended period of low temperature dormancy followed by exposure to warm temperatures. Yet the presence of sex steroid-concentrating neurons within the pathways regulating courtship and mating suggests that sex hormones may be involved in the activation of sexual behavior. Although circulating androgens are elevated upon emergence from hibernation, the initiation of courtship behavior and mating appears to be independent of direct androgen control. Thus steroid hormones may have indirect effects on mating behavior in animals that display "dissociated" reproductive behaviors.     

Hypertrophy of gonadotropin releasing hormone-containing neurons after castration in the teleost, Haplochromis burtoni.

In the African cichlid fish, Haplochromis burtoni, males are either territorial or nonterritorial. Territorial males suppress reproductive function in the nonterritorial males, and have larger gonads and larger gonadotropin-releasing hormone- (GnRH) containing neurons in the preoptic area (POA). We describe an experiment designed to establish the causal relationship between large GnRH neurons and large testes in these males by determining the feedback effects of gonadal sex steroids on the GnRH neurons. Territorial males were either castrated or sham-operated, 4 weeks after which they were sacrificed. Circulating steroid levels were measured, and the GnRH-containing neurons were visualized by staining sagittal sections of the brains with an antibody to salmon GnRH. The soma areas of antibody-stained neurons were measured with a computer-aided imaging system. Completely castrated males had markedly reduced levels of circulating sex steroids [11-ketotestosterone (11KT) and testosterone (T)], as well as 17 beta-estradiol (E2). POA GnRH neurons in castrates showed a significant increase in mean soma size relative to the intact territorial males. Hence, in mature animals, gonadal steroids act as a brake on the growth of GnRH-containing neurons, and gonadal products are not responsible for the large GnRH neurons characteristic of territorial males.     

Circulating LH levels and the response to exogenous GnRH in the common mole-rat: implications for reproductive regulation in this social, seasonal breeding species

The effects of breeding season and reproductive status on male and female reproduction were investigated in the common mole-rat, Cryptomys hottentotus hottentotus, a cooperatively breeding rodent which exhibits a unique combination of seasonal breeding and a reproductive division of labor. Pituitary function was examined by measuring the luteinizing hormone (LH) responses to single doses of 2 microg exogenous gonadotrophin-releasing hormone (GnRH) and physiological saline in 69 males and 58 females from 35 wild caught colonies. Neither males nor females exhibited any apparent manifestation of season on basal LH concentrations or on pituitary sensitivity to stimulation by exogenous GnRH. The continuance of reproductive function during the nonbreeding period is essential in common mole-rat males and females, as this period coincides with the period of maximal dispersal opportunity in the winter rainfall area they inhabit. Normal circulating levels of reproductive hormones in dispersing animals may aid intersexual recognition, assist pairbond formation, and thus prime animals for independent reproduction. Circulating basal concentrations of LH as well as LH levels measured in response to a single exogenous GnRH challenge were not significantly different between the reproductive and non-reproductive groups of either sex, suggest the absence of a physiologically well-defined suppression of reproduction in subordinate common mole-rats.     

Reproductive suppression in eusocial Cryptomys darnavensis colonies: socially-induced infertility in females

Inhibition of reproduction occurs in colonies of the Damaraland mole-rat ( Cryptomys damarensis ), where one female and usually one male are reproductively active. They remain the sole reproductive animals thoughout their stay in the colony, which in the field may exceed five years.
An 18-month study on a captive colony of C. damarensis shows that non-reproductive females remain anovulatory and always have concentrations of urinary progesterone lower than that of the reproductive female 10.7 8.8 nmols/mmol creatinine (n = 85), although their progesterone concentrations are slightly elevated when the reproductive female is early in pregnancy. In contrast the reproductively active female has elevated concentrations of progesterone 63.3 70.1 nmols/mmol creatinine (n= 14).
Standard histological together with immunohistochemical examination of the ovarian structure shows that follicular development in the non-reproductive females is halted at varying stages prior to ovulation and that the unruptured follicles luteinize. These unruptured luteinized follicles stain positive for 3β hydroxysteroid dehydrogenase—the enzyme catalysing the synthesis of progesterone from pregnenolone. It is possible that the low levels of circulating progesterone produced by the luteinized follicles in the non-reproductive females in the colony are sufficient to feedback on the hypothalamo-pituitary axis and prevent the surge of LH necessary for ovulation.
Behavioural studies provide corroborative evidence for sexual suppression. Thus the non-reproductive females in the colony are never involved in courtship or copulatory behaviour. nor do they actively solicit males in the colony. The reproductive female, however, plays an active role in mate selection and is the initiator in courtship behaviour.
The suppression of ovulation in non-reproductivc females is maintained for as long as there is a reproductive female in the colony.     

Mechanisms of sex steroid effects on bone

Sex steroids play a major role in the regulation of bone turnover. Thus, gonadectomy in either sex is associated with an increase in bone remodeling, increased bone resorption, and a relative deficit in bone formation, resulting in accelerated bone loss. Recent physiological studies have established an important role for estrogen in regulating bone turnover not only in females, but also in males. Studies in mice with knock out of the estrogen receptor, aromatase, or androgen receptor have provided important insights into the in vivo mechanisms of sex steroid action on bone. The cellular and molecular mediators of sex steroid effects on the bone-forming osteoblasts and bone-resorbing osteoclasts are also being increasingly better defined. Estrogen inhibits bone remodeling by concurrently suppressing osteoblastogenesis and osteoclastogenesis from marrow precursors. Both estrogen and androgens inhibit bone resorption via effects on the receptor activator of NF-kappaB ligand (RANKL)/RANK/osteoprotegerin system, as well as by reducing the production of a number of pro-resorptive cytokines, along with direct effects on osteoclast activity and lifespan. Sex steroid effects on bone formation are also likely mediated by multiple mechanisms, including a prolongation of osteoblast lifespan via non-genotropic mechanisms, as well as effects on osteoblast differentiation and function. These pleiotropic actions of sex steroids on virtually all aspects of bone metabolism belie the importance of the skeleton not only in providing structural support for the body and in locomotion, but also as a dynamic tissue responsive, among other things, to the reproductive needs of the organism for calcium.     

Influence of sex-specific stimuli on ovarian maturation in primary and secondary reproductives of the dampwood termite Zootermopsis angusticollis

Abstract. It was hypothesized that female primary and secondary reproductives of the termite Zootermopsis angusticollis Hagen require sex-specific stimuli from a reproductive male to trigger ovarian maturation. To test this hypothesis, experimental laboratory colonies were established that contained female primary or secondary reproductives nesting: alone; with a male; with a female; and with three third- to fourth-instar larvae. Following colony initiation, we measured changes in body mass, ovariole number and fecundity over 60 days. Results indicate that the reproductive maturation of female primaries was promoted by contact with a male but inhibited by the presence of another female. Secondary females were not affected by the presence of another reproductive, regardless of sex, but the development of reproductive competency of primary females appeared to depend on male-specific stimulation. Reliance on male–female interaction to induce female reproductive development may ensure that the resources of newly dealate females are not wasted on producing larvae that would have a poor chance of surviving in the absence of a male. By contrast, secondary females maturing within established colonies are likely to have a mate and immediate assistance with non-reproductive tasks, and therefore do not delay ovarian maturation and reproduction until they perceive male-specific stimuli. These results demonstrate that male-specific stimuli affect only the reproductive development of primary females, and suggest that the degree to which primary and secondary females depend on mate assistance may have shaped their physiological responses to the presence of a reproductive male.     

Do mollusks use vertebrate sex steroids as reproductive hormones? II. Critical review of the evidence that steroids have biological effects

In assessing the evidence as to whether vertebrate sex steroids (e.g. testosterone, estradiol, progesterone) have hormonal actions in mollusks, ca. 85% of research papers report at least one biological effect; and 18 out of 21 review papers (published between 1970 and 2012) express a positive view. However, just under half of the research studies can be rejected on the grounds that they did not actually test steroids, but compounds or mixtures that were only presumed to behave as steroids (or modulators of steroids) on the basis of their effects in vertebrates (e.g. Bisphenol-A, nonylphenol and sewage treatment effluents). Of the remaining 55 papers, some can be criticized for having no statistical analysis; some for using only a single dose of steroid; others for having irregular dose–response curves; 40 out of the 55 for not replicating the treatments; and 50 out of 55 for having no within-study repetition. Furthermore, most studies had very low effect sizes in comparison to fish-based bioassays for steroids (i.e. they had a very weak ‘signal-to-noise’ ratio). When these facts are combined with the fact that none of the studies were conducted with rigorous randomization or ‘blinding’ procedures (implying the possibility of ‘operator bias’) one must conclude that there is no indisputable bioassay evidence that vertebrate sex steroids have endocrinological or reproductive roles in mollusks. The only observation that has been independently validated is the ability of estradiol to trigger rapid (1–5 min) lysosomal membrane breakdown in hemocytes of Mytilus spp. This is a typical ‘inflammatory’ response, however, and is not proof that estradiol is a hormone – especially when taken in conjunction with the evidence (discussed in a previous review) that mollusks have neither the enzymes necessary to synthesize vertebrate steroids nor nuclear receptors with which to respond to them.     

Sex-based differences in physiology: what should we teach in the medical curriculum?

An abundance of recent research indicates that there are multiple differences between males and females both in normal physiology and in the pathophysiology of disease. The Refresher Course on Gender Differences in Physiology, sponsored by the American Physiological Society Education Committee at the 2006 Experimental Biology Meeting in San Franciso, CA, was designed to provide teachers of medical physiology with the background necessary to include the most important aspects of sex-based differences in their curricula. The presentations addressed sex-based differences in the physiology and pathophysiology of the cardiovascular, musculoskeletal, and immune systems as well as the cellular mechanisms of sex steroid hormone actions on non-reproductive tissues. The slides and audio files for these presentations are available at http://www.the-aps.org/education/refresher/index.htm. This overview highlights the key concepts relevant to the topic of sex-based differences in physiology: why these differences are important, their potential causes, and examples of prominent differences between males and females in normal physiological function for selected organ systems.     

Life History Dependent Behavioural Variation in Water Striders,Aquarius remigis

We investigated behavioural consequences of life history states in Aquarius (Gerris) remigis, a hemipteran surface predator and scavenger of small North American streams. A repeated-measures field study comparing reproductive and non-reproductive first summer generation females and males during the same time in summer showed that non-reproductive males and females, which were foraging to survive the winter, behaved essentially alike, often being territorial. In contrast, reproductives of both sexes were more mobile than non-reproductives, reproductive males being much more mobile than reproductive females, always in search of and attacking potential mates. This resulted in reproductive males showing litde territoriality and having lower foraging success than all other categories, while reproductive females had higher foraging success than non-reproductive females or males, thus likely increasing their fecundity. Many behavioural variables did not change with time. Exceptions were a decrease in the mating activity of reproductives of both sexes, the number of mating attempts, mobility, and the stride rate of reproductive males, and an increase in overall foraging activity of all individuals. This indicates that the behaviour of reproductive males converged towards that of non-reproductive males as the season progressed. Individuals were assigned to either state post-hoc according to whether they had been seen mating at least once during the study period (July and August). Females were further tested to ascertain if they laid eggs. These results support the hypothesis that diapause and reproductive state to some degree predetermine behaviour, thus constraining behavioural flexibility. Attributing behavioural variation to various proximate causes can be central to the interpretation of alternative strategies and tactics.     

The physiology of follicular maturation in the pig

Exogenous gonadotrophin (eg. PMSG) treatment results in follicular growth in most reproductive states, and suggests that lack of FSH and LH-like activity is a likely cause of arrested-follicular development in the pig. Endogenous changes in gonadotrophins between reproductive and non-reproductive states are consistent with this concept. However, changes in the pattern of LH secretion, rather than clearly defined changes in FSH release, appear to be the effective trigger for follicular recruitment. In other situations in vivo, follicular growth is initiated in the absence of demonstrable changes in LH or FSH secretion, suggesting that other hormones interact to sensitize the ovary to gonadotrophins. Such effects have been reported for insulin, cortisol, thyroxine and IGF-1 in vitro, and the steroid environment of follicles also affects gonadotrophin receptors and receptor-mediated mechanisms. Once initiated, the regulation of follicle maturation also involves interactions between gonadotrophins and steroids, as well as other intra-ovarian regulators. Co-operation exists between theca and granulosa in the synthesis of steroids and androgen precursor availability is an important regulator of the oestrogenic activity of follicles. Considerable heterogeneity exists in the morphological and biochemical maturity of preovulatory follicles and inter-follicular regulation via endocrine and paracrine mechanisms may be an essential component of the selection process.     

Hypertrophy of gonadotropin releasing hormone-containing neurons after castration in the teleost,Haplochromis burtoni

In the African cichlid fish, Haplochromis burtoni, males are either territorial or nonterritorial. Territorial males suppress reproductive function in the nonterritorial males, and have larger gonads and larger gonadotropin-releasing hormone- (GnRH) containing neurons in the preoptic area (POA). We describe an experiment designed to establish the causal relationship between large GnRH neurons and large testes in these males by determining the feedback effects of gonadal sex steroids on the GnRH neurons. Territorial males were either castrated or sham-operated, 4 weeks after which they were sacrificed. Circulating steroid levels were measured, and the GnRH-containing neurons were visualized by staining sagittal sections of the brains with an antibody to salmon GnRH. The soma areas of antibody-stained neurons were measured with a computer-aided imaging system. Completely castrated males had markedly reduced levels of circulating sex steroids [11-ketotestosterone (11 KT) and testosterone (T)], as well as 17β-estradiol (E₂). POA GnRH neurons in castrates showed a significant increase in mean soma size relative to the intact territorial males. Hence, in mature animals, gonadal steroids act as a brake on the growth of GnRH-containing neurons, and gonadal products are not responsible for the large GnRH neurons characteristic of territorial males. © 1992 John Wiley & Sons, Inc.     

Sexual abstinence and the cost of reproduction in adult male water snakes, Nerodia sipedon

Low frequency of reproduction among iteroparous organisms is most often observed among female ectothermic vertebrates and is thought to be a strategy used to defer reproductive costs. We assessed reproductive costs of male water snakes ( Nerodia sipedon ) to determine why half of adult males abstain from reproduction each year. There was no evidence of a short-term energetic cost of reproduction. Change in mass did not differ between reproductive and non-reproductive males during the one-month mating season or during the entire four-month activity season. Changes in mass of reproductive males were similar at two sites in which the spatial distribution of females differed. However, there were size-specific differences in growth and survival between reproductive and non-reproductive males. Among reproductive males growth rate decreased with body size at a lower rate than among non-reproductive males. Survival increased with body size for reproductive males, but decreased with body size among non-reproductive males. Most of the differential survival between reproductive and non-reproductive males did not occur during the mating season but rather during hibernation. Size-related differences between reproductive and non-reproductive males may reflect selection having eliminated low quality males from the larger size classes. Overall our results appear most consistent with there being high variance in male quality, such that the best males can bear the cost of reproducing and still grow and survive as well or better than low quality males that abstain from reproduction.     

The adjustment of reproductive threshold to prey abundance in a capital breeder

1. Many organisms rely upon stored energy reserves to support reproduction and do not initiate breeding until their reserves exceed some 'reproductive threshold'. However, the determinants of such thresholds are poorly understood; for example, we do not know if they are fixed (invariant) or respond dynamically to fluctuations in resource availability.
2. An 8-year field study on water pythons ( Liasis fuscus Peters 1873) in tropical Australia shows that individual female pythons adjust their reproductive thresholds in response to annual variation in prey abundance.
3. In every year of the study, female pythons that reproduced were in better condition (mass relative to body length) than non-reproductive females. However, in years with low abundance of rats, female pythons reproduced despite being in relatively poor condition. Indeed, the mean condition of reproductive pythons in one particularly 'bad' year was as low as the mean condition of non-reproductive females in a 'good' year.
4. Clutch sizes were slightly reduced in a 'bad' year, but the main effect of the lowered threshold was greater emaciation of the females after laying.
5. Recapture records of marked snakes show that the annual variation in thresholds is due to flexibility of individual females, not to differential representation of cohorts with different reproductive thresholds.
6. The dynamic adjustment of threshold levels fits well with predictions from life-history models and is likely to be a widespread phenomenon.     

Endocrine disruptors: present issues, future directions

A variety of natural products and synthetic chemicals, known collectively as endocrine-disrupting compounds (EDCs), mimic or interfere with the mechanisms that govern vertebrate reproductive development and function. At present, research has focused on (i) the morphological and functional consequences of EDCs; (ii) identifying and determining the relative potencies of synthetic and steroidal compounds that have endocrine-disrupting effects; (iii) the mechanism of action of EDCs at the molecular level; and (iv) the recognition that in "real life," contamination usually reflects mixtures of EDCs. Future research must examine (i) the interactive nature of EDCs, particularly whether the threshold concept as developed in traditional toxicological research applies to these chemicals; (ii) when and how EDCs act at the physiological level, particularly how they may organize the neural substrates of reproductive physiology and behavior; (iii) the various effects these compounds have on different species, individuals, and even tissues; and (iv) how adaptations may evolve in natural populations with continued exposure to EDCs. Several predictions are offered that reflect these new perspectives. Specifically, (i) the threshold assumption will be found not to apply to EDCs because they mimic the actions of endogenous molecules (e.g., estrogen) critical to development; hence, the threshold is automatically exceeded with exposure. (ii) Behavior can compound and magnify the effects of EDCs over successive generations; that is, bioaccumulated EDCs inherited from the mother not only influence the morphological and physiological development of the offspring but also the offsprings' reproductive behavior as adults. This adult behavior, in turn, can have further consequences on the sexual development of their own young. (iii) The sensitivity of a species or an individual to a compound is related to species (individual)-typical concentrations of circulating gonadal steroid hormones. Related to this is the recent finding that alternate forms of the putative receptors are differentially distributed, thereby contributing to the different effects that have been observed. (iv) Except in extraordinary situations, populations often continue to exist in contaminated sites. One possible explanation for this observation that needs to be considered is that animals can rapidly adapt to the nature and level of contamination in their environment. It is unlikely that successive generations coincidentally become insensitive to gonadal steroid hormones fundamentally important as biological regulators of development and reproduction. Rather, adaptive alterations in the genes that encode steroid receptors may occur with chronic exposure to EDCs, allowing the sex hormone receptor to discriminate natural steroids from EDCs.