Parent Hormone Research Articles

Prolactin and prolactin receptor expression in the HPG axis and crop during parental care in both sexes of a biparental bird (Columba livia)

During breeding, multiple circulating hormones, including prolactin, facilitate reproductive transitions in species that exhibit parental care. Prolactin underlies parental behaviors and related physiological changes across many vertebrates, including birds and mammals. While circulating prolactin levels often fluctuate across breeding, less is known about how relevant target tissues vary in their prolactin responsiveness via prolactin receptor (PRLR) expression. Recent studies have also investigated prolactin (PRL) gene expression outside of the pituitary (i.e., extra-pituitary PRL), but how PRL gene expression varies during parental care in non-pituitary tissue (e.g., hypothalamus, gonads) remains largely unknown. Further, it is unclear if and how tissue-specific PRL and PRLR vary between the sexes during biparental care. To address this, we measured PRL and PRLR gene expression in tissues relevant to parental care, the endocrine reproductive hypothalamic-pituitary- gonadal (HPG) axis and the crop (a tissue with a similar function as the mammalian mammary gland), across various reproductive stages in both sexes of a biparental bird, the rock dove (Columba livia). We also assessed how these genes responded to changes in offspring presence by adding chicks mid-incubation, simulating an early hatch when prolactin levels were still moderately low. We found that pituitary PRL expression showed similar increases as plasma prolactin levels, and detected extra-pituitary PRL in the hypothalamus, gonads and crop. Hypothalamic and gonadal PRLR expression also changed as birds began incubation. Crop PRLR expression correlated with plasma prolactin, peaking when chicks hatched. In response to replacing eggs with a novel chick mid-incubation, hypothalamic and gonadal PRL and PRLR gene expression differed significantly compared to mid-incubation controls, even when plasma prolactin levels did not differ. We also found sex differences in PRL and PRLR that suggest gene expression may allow males to compensate for lower levels in prolactin by upregulating PRLR in all tissues. Overall, this study advances our understanding of how tissue-specific changes in responsiveness to parental hormones may differ across key reproductive transitions, in response to offspring cues, and between the sexes.

Ovarian Hyperstimulation Syndrome Is Associated with a High Secondary Sex Ratio in Fresh IVF Cycles with Cleavage-Stage Embryo Transfer: Results for a Cohort Study.

The sex ratio at birth is defined as the secondary sex ratio (SSR). Ovarian hyperstimulation syndrome (OHSS) is a serious and iatrogenic complication associated with controlled ovarian stimulation (COS) during assisted reproductive technology (ART) treatments. It has been hypothesized that the human SSR is partially controlled by parental hormone levels around the time of conception. Given the aberrant hormonal profiles observed in patients with OHSS, this retrospective study was designed to evaluate the impact of OHSS on the SSR. In this study, all included patients were divided into 3 groups: non-OHSS (n=2777), mild OHSS (n=644), and moderate OHSS (n=334). Our results showed that the overall SSR for the study population was 1.033. The SSR was significantly increased in patients with moderate OHSS (1.336) compared to non-OHSS patients (1.002) (p=0.048). Subgroup analyses showed that increases in the SSR in patients with moderate OHSS were observed in the IVF group (1.323 vs 1.052; p=0.043), but not in the ICSI groups (1.021 vs 0.866; p=0.732). In addition, the elevated serum estradiol (E2) and progesterone (P4) levels in OHSS patients were not associated with SSR. In this study, for the first time, we report that a high SSR is associated with OHSS in patients who received fresh IVF treatments. The increases in SSR in OHSS patients are not attributed to the high serum E2 and P4 levels. Our findings may make both ART clinicians and patients more aware of the influences of ART treatments on the SSR and allow clinicians to counsel patients more appropriately.

Regulatory effects of prolactin on breeding and migratory behaviours in birds

Prolactin is an adenohypophyseal hormone of vertebrates produced by the neuroendocrine signaling of the hypothalamus. It plays important role in different vertebrate species and referred to as “The Parental Hormone” or “The Hormone of Maternity”. In birds the role of Prolactin is limited as the parental hormone but the behavioral functions like the regulation of season-al reproduction, combating stress of predators, nest building abilities and regulations of migratory cycle are diversified. The classical role of Prolactin in different birds’ species like pigeons and doves is secretion of crop sac “milk” after hatching of eggs and regulation of migration in different type of mi-grants. Reports have suggested that acute and chronic stressors and ener-getic constraints depress prolactin levels disrupting the parental effort in nest building, mate selection, incubation and crop milk production. Although prolactin is diverse in its function but acts through the same receptors throughout the vertebrate series. However, this review establishes that pro-lactin plays an intense role in regulating breeding behaviours and migration in birds along with the interactions of other hormones. Prolactin helps the birds to carry out wide range of behaviour and become evolutionarily suc-cessful.

Using conformational constraints at position 6 of Angiotensin II to generate compounds with enhanced AT2R selectivity and proteolytic stability

The Renin-Angiotensin System (RAS) plays a crucial role in numerous pathological conditions. Two of the critical RAS players, the angiotensin receptors AT1R and AT2R, possess differential functional profiles, although they share high sequence similarity. Although the main focus has been placed on AT1R, several epidemiological studies have evidenced that activation of AT2R could operate as a multimodal therapeutic target for different diseases. Thus, the development of selective AT2R ligands could have a high clinical potential for different therapeutic directions. Furthermore, they could serve as a powerful tool to interrogate the molecular mechanisms that are mediated by AT2R. Based on our recently established high affinity and AT2R selective compound [Y]6-AII we developed several analogues through modifying aminoacids located at positions 6 and 7 with various conformationally constrained analogues to enhance both the selectivity and stability. We report the development of high-affinity AT2R binders, which displayed high selectivity for AT2R versus AT1R. Furthermore, all analogues presented enhanced stability in human plasma with respect to the parent hormone Angiotensin II as also [Y]6-AII.

Markers of Local and Systemic Estrogen Metabolism in Endometriosis.

Estrogen metabolites (EMs) can work independently from their parent hormones. We hypothesize that in endometriosis, estrogen is metabolized preferentially along hormonally active pathways. We recruited 62 women with endometriosis (proven laparoscopically and histologically) and 52 control women (normal findings with laparoscopy) among patients undergoing surgery for pelvic pain and/or infertility during the proliferative phase of the menstrual cycle. Urinary samples were collected preoperatively. Biopsies from eutopic endometrium of control women and women with endometriosis were collected during surgery. EMs in urine and endometrial tissues were extracted and determined using Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (LC-ESI-MS/MS). These included: 2-hydroxyestrone (2OHE1), 16-α hydroxyestrone (16α-OHE1), 2OHE1/16α-OHE1 ratio, 4-hydroxyestrone (4OHE1), 2-hydroxyestradiol (2OHE2), and 4-hydroxyestradiol (4OHE2). Eutopic endometrium of endometriosis patients, as compared to control endometrium, contained significantly higher level of 4OHE1 (0.03 (IQR: 0.03-0.265) versus 0.03 (IQR: 0.03-0.03) μg/g, respectively, P = 0.005), 2-OHE2 (0.241 (IQR: 0.1-0.960) versus 0.1 (IQR: 0.1-0.1) μg/g, respectively, P < 0.001), and 4-OHE2 (0.225 (IQR: 0.22-1.29) versus 0.0.2 (IQR: 0.2-0.2) μg/g, respectively, P < 0.001). Only 2OHE1 showed higher concentration in urine of women with endometriosis than controls (9.9 (IQR: 3.64-14.88) versus 4.5 (IQR: 1.37-17.00) μg/mg creatinine, respectively, P = 0.042). Eutopic endometrium of women with endometriosis metabolizes estrogen preferentially to the biologically active 2OHE2, and potentially genotoxic 4OHE1 and 4OHE2 metabolites. This contributes to further understanding of endometriosis etiology, its link to ovarian cancer, and could help identifying an endometrial biomarker of the disease.

Strategies for the Synthesis of 19-nor-Vitamin D Analogs.

1α,25-Dihydroxyvitamin D3 [1α,25-(OH)2-D3], the hormonally active form of vitamin D3, classically regulates bone formation, calcium, and phosphate homeostasis. In addition, this hormone also exerts non-classical effects in a wide variety of target tissues and cell types, such as inhibition of the proliferation and stimulation of the differentiation of normal and malignant cells. However, to produce these actions, supraphysiological doses are required resulting in calcemic effects that limit the use of this natural hormone. During the past 30 years, many structurally modified analogs of the 1α,25-(OH)2-D3 have been synthesized in order to find derivatives that can dissociate the beneficial antiproliferative effects from undesired calcemic effects. Among these candidates, 1α,25-(OH)2-19-nor-D3 analogs have shown promise as good derivatives since they show equal or better activity relative to the parent hormone but with reduced calcemic effects. In this review, we describe the synthetic strategies to obtain the 19-nor-D3 derivatives and briefly describe their physiological activities.

Retina-Targeted Delivery of 17β-Estradiol by the Topically Applied DHED Prodrug.

The purpose of this study was to explore retina-targeted delivery of 17β-estradiol (E2), a powerful neuroprotectant, by its bioprecursor prodrug 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED) administered as eye drops in animal models. Compared to the parent hormone, DHED displayed increased transcorneal flux ex vivo both with and without the presence of 2-hydroxypropyl-β-cyclodextrin used as a penetration-enhancing excipient in rat, rabbit, and pig. In vitro, the prodrug also showed facile bioactivation to E2 in the retina but not in the cornea. After topical administration to rats and rabbits, peak DHED-derived E2 concentrations reached 13 ± 5 ng/g and 18 ± 7 ng/g in the retina of female rats and rabbits, respectively. However, the prodrug remained inert in the rest of the body and, therefore, did not cause increase in circulating hormone concentration, as well as wet uterine and anterior pituitary weights as typical markers of E2′s endocrine impact. Altogether, our studies presented here have demonstrated the premise of topical retina-selective estrogen therapy by the DHED prodrug approach for the first time and provide compelling support for further investigation into the full potential of DHED for an efficacious and safe ocular neurotherapy.

It takes two! Exploring sex differences in parenting neurobiology and behaviour.

Parents lay the foundation for their children's socio-emotional experiences by sensitively responding to their needs. The hormonal and neurobiological changes that occur during the transition to parenthood importantly contribute to the parents' caregiving behaviour toward their children. Much research has emphasised the relationship between the mother, who is most often the primary caregiver, and her infant, with less focus on the role of fathers in child development. However, recent accounts have suggested that fathers also play an important role in promoting the health, development and psychosocial wellbeing of their children. Evidence from the behavioural literature has indicated that there are significant differences between typical mother-infant versus father-infant interactions. The current review aims to outline differences between maternal and paternal caregiving by discussing the differences in their biological mechanisms. First, we focus on the different hormones that are correlated with sensitive parenting behaviours in mothers and fathers. Next, we discuss the differences between neural bases of motherhood and fatherhood. Lastly, we discuss ways in which parental hormones, parental brain and parental exposure to infant cues interact to shape parental caregiving behaviour. In summary, this review highlights the distinct but complementary nature of maternal and paternal caregiving.

Vitamins D: Relationship between Structure and Biological Activity.

The most active metabolite of vitamin D is 1α,25-dihydroxyvitamin D3, which is a central regulator of mineral homeostasis: excessive administration leads to hypercalcemia. Additionally, 1α,25-dihydroxyvitamin D3 is important to decision-making by cells, driving many cell types to growth arrest, differentiate and undergo apoptosis. 1α,25-Dihydroxyvitamin D3 regulates gene transcription by binding to a single known receptor, the vitamin D receptor. Rapid intracellular signals are also elicited in vitro by 1α,25-dihydroxyvitamin D3 that are independent of transcription. There are many aspects of the multiple actions of 1α,25-dihydroxyvitamin D3 that we do not fully understand. These include how a single receptor and provoked rapid events relate to the different actions of 1α,25-dihydroxyvitamin D3, its calcemic action per se, and whether a large number of genes are activated directly, via the vitamin D receptor, or indirectly. A strategy to resolving these issues has been to generate synthetic analogues of 1α,25-dihydroxyvitamin D3: Some of these separate the anti-proliferative and calcemic actions of the parent hormone. Crystallography is important to understanding how differences between 1α,25-dihydroxyvitamin D3- and analogue-provoked structural changes to the vitamin D receptor may underlie their different activity profiles. Current crystallographic resolution has not revealed such information. Studies of our new analogues have revealed the importance of the A-ring adopting the chair β-conformation upon interaction with the vitamin D receptor to receptor-affinity and biological activity. Vitamin D analogues are useful probes to providing a better understanding of the physiology of vitamin D.

Reproduction impairments in metal-polluted environments and parental hormones: No evidence for a causal association in an experimental study in breeding feral pigeons exposed to lead and zinc

Humans are responsible for land-cover changes resulting in the emission of hazardous chemical elements including metallic trace elements i.e. MTEs. As a consequence, urban wildlife is exposed to high concentrations of MTEs, which exposure is linked to reproductive impairments. MTE effects on reproduction outputs might result from MTE exposure disrupting the endocrine pathways involved in reproductive behaviours. In birds, there is strong evidence that prolactin, corticosterone and testosterone are all involved in the regulation of parental effort during incubation and chick rearing. Endocrine-disrupting chemicals might stimulate or inhibit the production of those hormones and consequently alter parental investment and reproductive success outcomes. We measured baseline corticosterone, prolactin and testosterone plasma levels, and the corticosterone stress response of breeding feral pigeons (Columba livia) experimentally exposed to ecologically relevant lead and/or zinc concentrations. Independently of lead and/or zinc exposure, male and female plasma levels of corticosterone and prolactin (but not testosterone) showed temporal variations along the reproduction stages (i.e. incubation, early rearing and late rearing). In addition, both hatching and fledging success were slightly correlated with corticosterone, prolactin and testosterone levels. However, our study did not find any influence of lead or zinc exposure on hormone levels, suggesting that MTE effects on reproductive outputs might not be explained by MTE-induced modifications of corticosterone, prolactin and testosterone-linked behaviours during incubation and rearing. Alternatively, MTE-induced reproductive impairments might result from MTE exposure having direct effects on offspring phenotypes or prenatal indirect effects on the embryo (e.g. maternal transfer of MTEs, hormones or immune compounds).

Parental hormones are associated with crop loss and family sickness following catastrophic flooding in lowland Bolivia

The physiology of fatherhood is a growing field of study, and variability in hormonal mediators of reproductive effort (e.g. testosterone, cortisol) can predict variability in paternal investment. Studies often find that lower testosterone levels are associated with increased paternal investment, though most studies are conducted under relatively stable ecological conditions. In this paper, we examine parental physiological correlates of crop loss and family health problems among Tsimane forager-horticulturalists following a catastrophic flood in lowland Bolivia. Immediately after a devastating 2014 flood that impacted >75% of Tsimane communities, we conducted structured interviews examining crop losses and morbidity, and collected saliva specimens from 421 parents (n = 292 households) to analyze cortisol and testosterone. Over 98% of interviewees reported horticultural losses, with the average family losing 88% of their crops, while 80% of families reported flood-induced injuries or illnesses. Controlling for age, body mass index, and time of specimen collection, men's testosterone was negatively associated with both absolute cropland losses (Std. β = −0.16, p = 0.037), and percent of cropland lost (Std. β = −0.16, p = 0.040). Female testosterone was not associated with crop losses. Using the same control variables, both male and female cortisol was negatively associated with a composite measure of child health burden (fathers: Std. β = −0.34, p < 0.001; mothers: Std. β = −0.23, p = 0.037). These results are discussed in the cultural context of a strong sexual division of labor among Tsimane; we highlight the physiological and psychosocial costs of experiencing a natural disaster, especially for paternal caregivers in a nutritionally and pathogenically stressed subsistence population where cultigens provide the majority of calories in the diet.

Tetrac downregulates β-catenin and HMGA2 to promote the effect of resveratrol in colon cancer.

The molecular pathogenesis of colorectal cancer encompasses the activation of several oncogenic signaling pathways that include the Wnt/β-catenin pathway and the overexpression of high mobility group protein A2 (HMGA2). Resveratrol - the polyphenolic phytoalexin - binds to integrin αvβ3 to induce apoptosis in cancer cells via cyclooxygenase 2 (COX-2) nuclear accumulation and p53-dependent apoptosis. Tetraiodothyroacetic acid (tetrac) is a de-aminated derivative of l-thyroxine (T4), which - in contrast to the parental hormone - impairs cancer cell proliferation. In the current study, we found that tetrac promoted resveratrol-induced anti-proliferation in colon cancer cell lines, in primary cultures of colon cancer cells, and in vivo The mechanisms implicated in this action involved the downregulation of nuclear β-catenin and HMGA2, which are capable of compromising resveratrol-induced COX-2 nuclear translocation. Silencing of either β-catenin or HMGA2 promoted resveratrol-induced anti-proliferation and COX-2 nuclear accumulation which is essential for integrin αvβ3-mediated-resveratrol-induced apoptosis in cancer cells. Concurrently, tetrac enhanced nuclear abundance of chibby family member 1, the nuclear β-catenin antagonist, which may further compromise the nuclear β-catenin-dependent gene expression and proliferation. Taken together, these results suggest that tetrac targets β-catenin and HMGA2 to promote resveratrol-induced-anti-proliferation in colon cancers, highlighting its potential in anti-cancer combination therapy.

Convergent ERK1/2, p38 and JNK mitogen activated protein kinases (MAPKs) signalling mediate catecholoestradiol-induced proliferation of ovine uterine artery endothelial cells.

The catechol metabolites of 17β-oestradiol (E2 β), 2-hydroxyoestradiol (2-OHE2 ) and 4-hydroxyoestradiol (4-OHE2 ), stimulate proliferation of pregnancy-derived ovine uterine artery endothelial cells (P-UAECs) through β-adrenoceptors (β-ARs) and independently of the classic oestrogen receptors (ERs). Herein we show that activation of ERK1/2, p38 and JNK mitogen activated protein kinases (MAPKs) is necessary for 2-OHE2 - and 4-OHE2 -induced P-UAEC proliferation, as well as proliferation induced by the parent hormone E2 β and other β-AR signalling hormones (i.e. catecholamines). Conversely, although 2-OHE2 and 4-OHE2 rapidly activate phosphatidylinositol 3-kinase (PI3K), its activation is not involved in catecholoestradiol-induced P-UAEC proliferation. We also show for the first time the signalling mechanisms involved in catecholoestradiol-induced P-UAEC proliferation; which converge at the level of MAPKs with the signalling mechanisms mediating E2 β- and catecholamine-induced proliferation. The present study advances our understanding of the complex signalling mechanisms involved in regulating uterine endothelial cell proliferation during pregnancy. Previously we demonstrated that the biologically active metabolites of 17β-oestradiol, 2-hydroxyoestradiol (2-OHE2 ) and 4-hydroxyoestradiol (4-OHE2 ), stimulate pregnancy-specific proliferation of uterine artery endothelial cells derived from pregnant (P-UAECs), but not non-pregnant ewes. However, unlike 17β-oestradiol, which induces proliferation via oestrogen receptor-β (ER-β), the catecholoestradiols mediate P-UAEC proliferation via β-adrenoceptors (β-AR) and independently of classic oestrogen receptors. Herein, we aim to further elucidate the signalling mechanisms involved in proliferation induced by catecholoestradiols in P-UAECs. P-UAECs were treated with 2-OHE2 and 4-OHE2 for 0, 0.25, 0.5, 1, 2, 4, 12 and 24h, to analyse activation of mitogen activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K)-AKT. Specific inhibitors for ERK1/2 MAPK (PD98059), p38 MAPK (SB203580), JNK MAPK (SP600125), or PI3K (LY294002) were used to determine the involvement of individual kinases in agonist-induced P-UAEC proliferation. 2-OHE2 and 4-OHE2 stimulated biphasic phosphorylation of ERK1/2, slow p38 and JNK phosphorylation over time, and rapid monophasic AKT phosphorylation. Furthermore, ERK1/2, p38 and JNK MAPKs, but not PI3K, were individually necessary for catecholoestradiol-induced proliferation. In addition, when comparing the signalling mechanisms of the catecholoestradiols, to 17β-oestradiol and catecholamines, we observed that convergent MAPKs signalling pathways facilitate P-UAEC proliferation induced by all of these hormones. Thus, all three members of the MAPK family mediate the mitogenic effects of catecholoestradiols in the endothelium during pregnancy. Furthermore, the convergent signalling of MAPKs involved in catecholoestradiol-, 17β-oestradiol- and catecholamine-induced endothelial cell proliferation may be indicative of unappreciated evolutionary functional redundancy to facilitate angiogenesis and ensure maintenance of uterine blood flow during pregnancy.

A comparative evaluation of treatments with 17β-estradiol and its brain-selective prodrug in a double-transgenic mouse model of Alzheimer's disease

Estrogens are neuroprotective and, thus, potentially useful for the therapy of Alzheimer's disease; however, clinical use of hormone therapy remains controversial due to adverse peripheral effects. The goal of this study was to investigate the benefits of treatment with 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), a brain-selective prodrug of 17β-estradiol, in comparison with the parent hormone using APPswe/PS1dE9 double transgenic mice to model the pathology of the disease. Ovariectomized and intact females were continuously treated with vehicle, 17β-estradiol, or DHED via subcutaneous osmotic pumps from 6 to 8months of age. We confirmed that this prolonged treatment with DHED did not stimulate uterine tissue, whereas 17β-estradiol treatment increased uterine weight. Amyloid precursor protein decreased in both treatment groups of intact, but not in ovariectomized double transgenic females in which ovariectomy already decreased the expression of this protein significantly. However, reduced brain amyloid-β peptide levels could be observed for both treatments. Consequently, double-transgenic ovariectomized and intact mice had higher cognitive performance compared to untreated control animals in response to both estradiol and DHED administrations. Overall, the tested brain-selective 17β-estradiol prodrug proved to be an effective early-stage intervention in an Alzheimer's disease-relevant mouse model without showing systemic impact and, thus, warrants further evaluation as a potential therapeutic candidate.

Biological Evaluation of Double Point Modified Analogues of 1,25-Dihydroxyvitamin D₂ as Potential Anti-Leukemic Agents.

Structurally similar double-point modified analogues of 1,25-dihydroxyvitamin D2 (1,25D2) were screened in vitro for their pro-differentiating activity against the promyeloid cell line HL60. Their affinities towards human full length vitamin D receptor (VDR) and metabolic stability against human vitamin D 24-hydroxylase (CYP24A1) were also tested. The analogues (PRI-1730, PRI-1731, PRI-1732, PRI-1733 and PRI-1734) contained 5,6-trans modification of the A-ring and of the triene system, additional hydroxyl or unsaturation at C-22 in the side chain and reversed absolute configuration (24-epi) at C-24 of 1,25D2. As presented in this paper, introduction of selected structural modifications simultaneously in two distinct parts of the vitamin D molecule resulted in a divergent group of analogues. Analogues showed lower VDR affinity in comparison to that of the parent hormones, 1,25D2 and 1,25D3, and they caused effective HL60 cell differentiation only at high concentrations of 100 nM and above. Unexpectedly, introducing of a 5,6-trans modification combined with C-22 hydroxyl and 24-epi configuration switched off entirely the cell differentiation activity of the analogue (PRI-1734). However, this analogue remained a moderate substrate for CYP24A1, as it was metabolized at 22%, compared to 35% for 1,25D2. Other analogues from this series were either less (12% for PRI-1731 and PRI-1733) or more (52% for PRI-1732) resistant to the enzymatic deactivation. Although the inactive analogue PRI-1734 failed to show VDR antagonism, when tested in HL60 cells, its structure might be a good starting point for our design of a vitamin D antagonist.

Get the most out of blow hormones: validation of sampling materials, field storage and extraction techniques for whale respiratory vapour samples.

Studies are progressively showing that vital physiological data may be contained in the respiratory vapour (blow) of cetaceans. Nonetheless, fundamental methodological issues need to be addressed before hormone analysis of blow can become a reliable technique. In this study, we performed controlled experiments in a laboratory setting, using known doses of pure parent hormones, to validate several technical factors that may play a crucial role in hormone analyses. We evaluated the following factors: (i)practical field storage of samples on small boats during daylong trips; (ii)efficiency of hormone extraction methods; and (iii)assay interference of different sampler types (i.e. veil nylon, nitex nylon mesh and polystyrene dish). Sampling materials were dosed with mock blow samples of known mixed hormone concentrations (progesterone, 17β-estradiol, testosterone, cortisol, aldosterone and triiodothyronine), designed to mimic endocrine profiles characteristic of pregnant females, adult males, an adrenal glucocorticoid response or a zero-hormone control (distilled H2O). Results showed that storage of samples in a cooler on ice preserved hormone integrity for at least 6 h (P=0.18). All sampling materials and extraction methods yielded the correct relative patterns for all six hormones. However, veil and nitex mesh produced detectable assay interference (mean 0.22±0.04 and 0.18±0.03 ng/ml, respectively), possibly caused by some nylon-based component affecting antibody binding. Polystyrene dishes were the most efficacious sampler for accuracy and precision (P<0.001), but required an ethanol rinse for improved progesterone recovery (increased 81%; P<0.001). Awareness of assay interference from exogenous materials is crucial to future studies. This study establishes critical groundwork to help ensure that hormones can be measured accurately in samples obtained from field collections of whale blow.

Does prolactin mediate parental and life-history decisions in response to environmental conditions in birds? A review

This article is part of a Special Issue “Parental Care”. In vertebrates, adjustments of physiology and behavior to environmental changes are often mediated by central physiological mechanisms, and more specifically by hormonal mechanisms. As a consequence, these mechanisms are thought to orchestrate life-history decisions in wild vertebrates. For instance, investigating the hormonal regulation of parental behavior is relevant to evaluate how parents modulate their effort according to specific environmental conditions. Surprisingly and despite being classically known as the ‘parental hormone’, prolactin has been overlooked in birds relative to this context. Our aim is to review evidence that changes in prolactin levels can mediate, at least to some extent, the response of breeding birds to environmental conditions. To do so, we first examine current evidence and limits for the role of prolactin in mediating parental behavior in birds. Second, we emphasize the influence of environmental conditions and stressors on circulating prolactin levels. In addition, we review to what extent prolactin levels are a reliable predictor of breeding success in wild birds. By linking environmental conditions, prolactin regulation, parental behavior, and breeding success, we highlight the potential role of this hormone in mediating parental decisions in birds. Finally, we also review the potential role of prolactin in mediating other life history decisions such as clutch size, re-nesting, and the timing of molt. By evaluating the influence of stressors on circulating prolactin levels during these other life-history decisions, we also raise new hypotheses regarding the potential of the prolactin stress response to regulate the orchestration of the annual cycle when environmental changes occur. To sum up, we show in this review that prolactin regulation has a strong potential to allow ecological physiologists to better understand how individuals adjust their life-history decisions (clutch size, parental behavior, re-nesting, and onset of molt) according to the environmental conditions they encounter and we encourage further research on that topic.

If everyone wanted girls more boys might be born

In the July 2011 Gazette Paseau [1] considers a population in which each birth is an independent event with probability g of being a girl and b of being a boy (b + g = 1). He supposes that, due to a preference for girls, all couples stop after producing k girls, where k is an integer greater or equal to 1. Each new birth will, even after some couples have stopped producing, still have the probability g of being a girl and b of being a boy. Paseau correctly states and shows that this will mean that the ratioExpected number of girl births : Expected number of boy births is g : b.So it is the same as if all couples stopped randomly. Paseau was showing that this result was a consequence of the ratio g : b always being the same for all families.However in humans the ratio g : b is not always the same. The ratio g : b can vary significantly with many variables between couples, which influence either the ratio at conception or the subsequent implantation and survival of male or female foetuses to birth. For example, mothers whose menstrual cycles have a short follicular phase (normally days 1-14 of the 28-day cycle) tend to produce boys [2], resulting in a smaller g : b ratio. Also the timing of insemination within the menstrual cycle is associated with the gender outcome such that insemination early or late in the fertile period means that the offspring is more likely to be male; if insemination occurs in the middle it is more likely to be female [3]. It is therefore likely that changes in parental hormone concentrations during the fertile period can affect the sexes of the children [4].

Catechol estrogens induce proliferation and malignant transformation in prostate epithelial cells

In the current study, the non-transformed prostatic epithelial cells (BPH-1) were exposed to the catechol estrogens (CE) 2-hydroxyestradiol (2-OHE2) or 4-hydroxyestradiol (4-OHE2), or the parent hormone 17-β-estradiol (E2) at an equimolar concentration (1μM) for a period of 6 weeks. It was found that both 2-OHE2 and 4-OHE2 have more potent proliferation-enhancing effect than E2. Exposure to 2-OHE2, 4-OHE2 or E2 resulted in a significant increase in the protein abundance of cyclin D1 and c-myc. The treated cells exhibited a shift toward the proliferative phase as indicated by FACScan. BPH-1 cells treated with 4-OHE2 showed increased abundance of estrogen receptor-α (ERα) and its downstream IGF-1R. Reduced abundance of estrogen receptor-β (ERβ) and its downstream tumor suppressor FOXO-1 were observed in cells exposed to E2, 2-OHE2 and, to a greater extent, 4-OHE2. Comet assay revealed that CE, especially 4-OHE2, elicited significant genotoxic effects as compared to E2. 4-OHE2 showed greater ability to neoplastically transform BPH-1 cells as indicated by increased colony forming capacity in soft agar and matrix invasion. In conclusion, in vitro exposure to CE could neoplastically transform human prostatic epithelial cells. Further, 4-OHE2 is more carcinogenic to prostate epithelial cells than the parent hormone E2.

A comparative protease stability study of synthetic macrocyclic peptides that mimic two endocrine hormones

Peptide therapeutics have traditionally faced many challenges including low bioavailability, poor proteolytic stability and difficult cellular uptake. Conformationally constraining the backbone of a peptide into a macrocyclic ring often ameliorates these problems and allows for the development of a variety of new drugs. Such peptide-based pharmaceuticals can enhance the multi-faceted functionality of peptide side chains, permitting the peptides to bind cellular targets and receptors necessary to impart their role, while protecting them from degrading cellular influences. In the work described here, we developed three cyclic peptides, VP mimic1, VP mimic2 and OT mimic1, which mimic endocrine hormones vasopressin and oxytocin. Making notable changes to the overall structure and composition of the parent hormones, we synthesized the mimics and tested their durability against treatment with three proteases chosen for their specificity: pepsin, alpha-chymotrypsin, and pronase. Vasopressin and oxytocin contain a disulfide linkage leaving them particularly vulnerable to deactivation from the reducing environment inside the cell. Thus, we increased the complexity of our assays by adding reducing agent glutathione to each mixture. Subsequently, we discovered each of our mimics withstood protease treatment with less degradation and/or a slower rate of degradation as compared to both parent hormones and a linear control peptide.