Pituitary Responsiveness Research Articles

Efficiency of GnRH-Loaded Chitosan Nanoparticles for Inducing LH Secretion and Fertile Ovulations in Protocols for Artificial Insemination in Rabbit Does.

Simple SummaryNano-drug delivery systems can be employed for improving ovulation induction prior to artificial insemination (AI) in rabbits. In this study, different routes of administration and different doses of GnRH–loaded chitosan nanoparticles (GnRH–ChNPs) were assessed for inducing ovulation in rabbits, proving their usefulness to reduce the GnRH dose and animal handling and improving AI outcomes. The use of GnRH–ChNPs allows for the reduction of the conventional intramuscular GnRH dose to half without compromising fertility. However, the addition of GnRH–ChNPs to semen extenders, although successfully inducing ovulation, has negative impacts on fertility. Thus, more studies are needed to allow further adjustments.Gonadotropin-releasing hormone (GnRH)–loaded chitosan nanoparticles (GnRH–ChNPs) were used at different doses and routes of administration to induce ovulation in rabbits as an attempt to improve artificial insemination (AI) procedures and outcomes. In this study, the characteristics (size, polydispersity, loading efficiency, and zeta-potential) of GnRH–ChNPs and the GnRH release pattern were determined in an in vitro study. A first in vivo study assessed the pituitary and ovarian response to different GnRH–ChNPs doses and routes of administration (two i.m. doses, Group HM = 0.4 µg and Group QM = 0.2 µg, and two intravaginal doses, Group HV = 4 µg and Group QV = 2 µg) against a control group (C) receiving bare GnRH (0.8 µg). The HM, QM, and HV treatments induced an earlier LH-surge (90 min) than that observed in group C (120 min), whilst the QV treatment failed to induce such LH surge. The number of ovulation points was similar among treatments, except for the QV treatment (no ovulation points). A second in vivo study was consequently developed to determine the hormonal (progesterone, P4, and estradiol, E2) profile and pregnancy outcomes of both HM and HV treatments against group C. The treatment HM, but not the treatment HV, showed adequate P4 and E2 concentrations, conception and parturition rates, litter size, litter weight, and viability rate at birth. Overall, the use of GnRH–ChNPs allows for a reduction in the conventional intramuscular GnRH dose to half without compromising fertility. However, the addition of GnRH–ChNPs to semen extenders, although successfully inducing ovulation, has negative impacts on fertility. Thus, more studies are needed to explore this point and allow further adjustments.

89 Does progesterone block the nerve growth factor–induced luteinizing hormone surge in llamas?

The central inhibitory effects of progesterone on gonadotrophin secretion have been well documented in several species, including camelids. Nerve growth factor (NGF) in seminal plasma triggers ovulation in camelids and is thought to act at the level of the hypothalamus. The objective of the study was to determine the effect of progesterone on NGF-induced LH release in llamas. In Experiment 1, llamas were assigned to a low, medium, or high progesterone group (n=4 per group). The low progesterone group consisted of non-mated (non-ovulatory) llamas, the medium progesterone group consisted of mated llamas (luteal phase; 3–4 weeks pregnant), and the high progesterone group consisted of non-mated llamas given a single intramuscular (IM) dose of progesterone (300mg IM, Progesterone BioRelease LA). A jugular catheter was placed, and the following day llamas were given an intravenous dose of 1mg of NGF isolated from seminal plasma. Blood samples were taken every 30min from 1h before to 5.5h after NGF treatment. In Experiment 2, the pituitary LH response to gonadotrophin-releasing hormone (GnRH) was compared between llamas treated with either Progesterone BioRelease LA or saline (n=4 per group). Sixteen hours later, llamas in both groups were given 50µg of gonadorelin (GnRH) IV, and blood samples were collected by jugular puncture at 0.5h before and 0, 1, 2, and 4h after GnRH. Blood samples were centrifuged, and plasma was stored frozen until radioimmunoassay for LH and progesterone. Data are presented as mean±s.e.m. Data were analysed by one-way ANOVA for single-point and repeated-measures, and independent or paired t-tests. In Experiment 1, plasma progesterone concentrations in the low, medium, and high progesterone groups were 0.6±0.3, 8.2±0.4, and 14.9±1.2ng mL−1, respectively, at the time of NGF treatment (P<0.05). Circulating concentrations of LH did not differ among progesterone groups (treatment, P=0.49; time, P<0.01; treatment×time interaction, P=0.65). In all groups, LH concentrations were elevated within 30min of NGF administration, reached a peak by 2h, and remained elevated beyond the sampling period. Comparison of samples collected during the pretreatment period (i.e. −60, −30, and 0min), however, revealed that plasma LH concentrations in the high progesterone group were half that of the low and medium progesterone groups (P<0.03). In Experiment 2, plasma progesterone concentrations in the progesterone- and saline-treated groups were 12.7±2.2 and 1.3±0.3ngmL−1, respectively (P<0.01). Despite the difference in circulating progesterone concentrations, the LH response to GnRH treatment was not different between groups (treatment group, P=0.43; time, P<0.01; treatment×time interaction, P=0.84). Results demonstrate a suppressive effect of progesterone on basal LH release in llamas, but no suppressive effect on NGF- or GnRH-induced surge release from the pituitary gland. Results are consistent with the hypothesis that the site of action of NGF is downstream of the hypothalamic site of action of progesterone. This research was supported by NSERC Canada.

Soft drink intake on time of hypoglycaemia during insulin tolerance test: Effects on pituitary response and comfort for the patient

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

A Case Report of Pycnodysostosis Associated with Multiple Pituitary Hormone Deficiencies and Response to Treatment

A Case Report of Pycnodysostosis Associated with Multiple Pituitary Hormone Deficiencies and Response to Treatment

Nutritional and lactational effects on follicular development in the pig

In sows, follicular development is inhibited during lactation, and weaning the piglets allows recruitment and selection of follicles that will undergo preovulatory maturation and ovulate. Lactation inhibits GnRH secretion, and in turn LH secretion, through neuroendocrine stimuli induced by suckling. Pituitary response to GnRH and the sensitivity of the hypothalamo-pituitary unit to oestradiol positive feedback are also reduced. The impact of lactation on the reproductive axis is further complicated by the physiological and metabolic adaptations that are developed for milk production and that depend on nutrient intake, nutrient needs and body reserves. A strongly catabolic state during lactation amplifies the inhibition of LH secretion, thereby inducing a delay of oestrus and ovulation after weaning. Nevertheless, post-weaning ovulation is less delayed nowadays than in the 1970's or 80's. Nutritional deficiency has also deleterious effects on embryo survival, which are likely related to alterations in follicular growth and maturation. The physiological mechanisms by which information on the metabolic changes is transmitted to the hypothalamuspituitary- ovary axis are not fully understood in the sow. Glucose, insulin and leptin are the most likely signals informing the hypothalamus of the metabolic state, yet their roles have not been definitely established. At the ovarian level, folliculogenesis is likely to be altered by the reduction in insulin and IGF-I concentrations induced by nutritional deficiency. More knowledge is needed at the intrafollicular level to better understand nutritional effects on follicular development, and also on occyte quality and embryo development.

Seasonal effects on fertility in gilts and sows

The ancestral wild pig is a short day length seasonal breeder. The domestic pig appears to have retained some of this seasonality as evidenced by a reduction in fertility during the summer—autumn period. The most important aspect of this seasonality is a reduction in the number of mated sows that farrow. Many of these sows conceive and embryos develop normally for 20 - 25 days before pregnancy is terminated and the sow returns to oestrus (25 - 35 days after mating). In other species, transduction of photoperiodic information is achieved by release of melatonin during the dark period. In the pig, the pattern of melatonin secretion and the subsequent hypothalamo—pituitary—gonadal responses appear to be more complex. A relatively high light intensity is required for pigs to generate a distinct diurnal melatonin rhythm and they appear unable to respond appropriately to abrupt changes in photoperiod. Pigs on restricted feeding and maintained under long photoperiods (but not under short photoperiods) have higher concentrations of melatonin than do similarly maintained pigs fed ad libitum. Continuous release melatonin implants have a deleterious effect on farrowing rate, suggesting that the abnormally high melatonin concentrations observed in sows in summer—autumn play a role in the pathogenesis of seasonal infertility. Ad libitum feeding of sows during the first few weeks of pregnancy may prevent the increase in melatonin concentrations and so remove the seasonal influence on fertility. The pituitary response to different photoperiods is also somewhat confusing. Although there is some evidence of increased sensitivity to the negative feedback of ovarian steroids in the prepubertal gilts and weaned sows during summer—autumn, LH concentrations are increased in early pregnant sows. It is proposed that the failure of sows to maintain pregnancy in summer—autumn results from disruption of maternal recognition of pregnancy causing regression of the corpora lutea, loss of pregnancy and return of the sow to oestrus.

Molecular Mechanisms of Pituitary Cell Plasticity

The mechanisms that mediate plasticity in pituitary function have long been a subject of vigorous investigation. Early studies overcame technical barriers and challenged conceptual barriers to identify multipotential and multihormonal cell populations that contribute to diverse pituitary stress responses. Decades of intensive study have challenged the standard model of dedicated, cell type-specific hormone production and have revealed the malleable cellular fates that mediate pituitary responses. Ongoing studies at all levels, from animal physiology to molecular analyses, are identifying the mechanisms underlying this cellular plasticity. This review describes the findings from these studies that utilized state-of-the-art tools and techniques to identify mechanisms of plasticity throughout the pituitary and focuses on the insights brought to our understanding of pituitary function.

Copeptin response to hypoglycemic stress is linked to prolactin activation in children.

The physiological role of arginine vasopressin (AVP) in the acute stress response in humans and especially in children is unclear. The aim of this study was to explore the interaction between copeptin, a well-established surrogate marker of AVP release, and anterior pituitary hormone activation in response to acute hypoglycemic stress in children and adolescents. We conducted an exploratory single center study involving 77 children and adolescents undergoing insulin-induced hypoglycemia. Blood levels of copeptin, ACTH, cortisol, GH, prolactin, interleukin-6 (IL-6), adrenaline and noradrenaline were determined at baseline and after insulin-induced hypoglycemia. Basal plasma levels of copeptin (median: 5.2pmol/L) increased significantly after hypoglycemia (median 9.7pmol/L; P < 0.0001). Subjects with insufficient HPA axis response or severe GH deficiency had lower hypoglycemia-induced copeptin increase (median: 2.3pmol/L) compared with individuals with intact pituitary response (median: 5.2pmol/L, P = 0.02). Copeptin increase correlated significantly with the maximal increase of ACTH (rs = 0.30; P = 0.010), cortisol (rs = 0.33; P = 0.003), prolactin (rs = 0.25; P = 0.03), IL-6 (rs = 0.35; P = 0.008) and with BMI-SDS (rs = - 0.28, P = 0.01). In multivariate regression analysis, prolactin increase was the only independent variable associated with copeptin increase (P = 0.0004). Our data indicate that: (1) hypoglycemic stress elicits a marked copeptin response in children and adolescents, pointing out its role as an acute stress marker in this population; (2) stress-induced AVP/copeptin release is associated with anterior pituitary activation, mainly a prolactin response.

MON-270 Diagnostic Value of Copeptin in Central Diabetes Insipidus

Background: The diagnosis of diabetes insipidus (DI) relies on indirect measurement of serum and urine sodium and osmolality. Since the diagnosis can only be made when an inappropriately dilute urine is paired with a significantly concentrated serum, the process is tedious for the clinician and uncomfortable for the patient. Copeptin is the C-terminal portion of the anti-diuretic hormone (ADH) prohormone which correlates with the less stable ADH, therefore providing a direct measurement of posterior pituitary response to hyperosmolar stress. (1,2) Aim: This study aims to assess the diagnostic accuracy of copeptin in patients with central DI compared with subjects who underwent pituitary surgery without developing DI. Methods: Serum samples from subjects with central DI, control subjects post pituitary surgery with no DI (NDI) and control subjects with SIADH were collected and analysed on the BRAHMS KRYPTOR copeptin assay. Groups were compared using unpaired T-test and Levene’s test for equal variance. Results: 56 samples from 22 subjects (13 females, 9 males, mean age 53.9 ± 15.5 y.o.) were analysed. Two subjects had resolved DI (RDI) after copeptin analysis and were successfully weaned off DDAVP and reclassified as NDI. Of the DI subjects, 1 had acute and 5 had chronic DI. Copeptin was lower in DI compared to NDI group (p = 0.013), while serum sodium, osmolality, urine osmolality were similar. Copeptin did not differentiate between the SIADH and NDI groups. After exclusion of NDI samples with serum sodium ≤ 140 mmol/L, the area under the curve was 0.97 (95% CI 0.9 to 1.0), a copeptin cut-off of 2.9 pmol/L predicts DI with a sensitivity of 92% and a specificity of 90%. Conclusion: Copeptin concentration of < 3.0 pmol/L concurrently with serum sodium concentration of > 140mmol/L predicted central DI when using post pituitary surgery subjects without DI as controls.1. Winzeler, B., Zweifel, C., Nigro, N., Arici, B., Bally, M., Schuetz, P., Blum, C., Kelly, C., Berkmann, S., Huber, A., Gentili, F., Zadeh, G., Landolt, H., Mariani, L., Müller, B. and Christ-Crain, M. (2015). Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery. The Journal of Clinical Endocrinology & Metabolism, 100(6), pp.2275-2282.2. Fenske, J., Refardt, I., SchnyderI., Winzeler, B., Drummond J., Ribeiro-Oliveira, Jr. A., Drescher, T., Bilz S., Vogt, D.R., Malzahn, U., Kroiss, M., Christ, E., Henzen, C., Fischli S., Tönjes, A., Mueller, B., Schopohl, J., Flitsch, J., Brabant, G., Fassnacht M., Christ-Crain, M. (2018). Copeptin in the Diagnosis of Diabetes Insipidus. New England Journal of Medicine, 379(18), pp.1784-1786.

Interactions of circulating estradiol and progesterone on changes in endometrial area and pituitary responsiveness to GnRH†.

Changes in circulating progesterone (P4) and estradiol (E2) during proestrus produce dynamic changes in endometrial function and pituitary release of gonadotropins. Independent and combined effects of P4 and E2 on endometrium and pituitary were evaluated. In a preliminary study, an exogenous hormone model of proestrus was created by removal of corpus luteum and follicles ≥5mm followed by gradual removal of intravaginal P4 implants during 18h and treatment with increasing doses of estradiol benzoate during 48h to mimic proestrus using high E2 (n=9) or low E2 (n=9). Decreased P4, increased E2, and increased endometrial area (EA) simulated proestrus in high-E2 cows and this was used subsequently. The main experiment used a 2×2 factorial design with: high E2 and low P4 (n=11); high E2 and high P4 (n=11); low E2 and high P4 (n=11); low E2 and low P4 (n=10). At 48h, gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) and follicle stimulating hormone (FSH) release was determined. Variables were analyzed using PROCMIXED of Statistical Analysis System. The EA increased dramatically during 48h only in high-E2 and low-P4 cows. For FSH, high-E2 cows had greater area under the curve (AUC) and FSH peak after GnRH than low E2, with mild negative effects of high P4. For LH, concentration at peak and AUC were 2-fold greater in high E2 compared to low-E2 groups, with low P4 also 2-fold greater than high-P4 groups. Thus, maximal changes in uterus and pituitary during proestrus depend on both low P4 and high E2, but different physiologic responses are regulated differently by E2 and P4. Changes in endometrium depend on low P4 and high E2, whereas GnRH-induced FSH secretion primarily depends on high E2, and GnRH-induced LH secretion is independently increased by high E2 or reduced by high P4.

Adult height in short children born small for gestational age treated with growth hormone

Backgroundand objective Recombinant human growth hormone (rhGH) treatment in small for gestational age (SGA) children has been effective, although there is significant variability in the response. Adult height and the factors that determine the long-term response are evaluated. Patients and designA retrospective study of 80 patients born SGA with short stature treated with rhGH and followed until adult height (23 males). ResultsThe group starting treatment pre-puberty reached a higher Adult height (−1.4±0.6 vs. −1.9±.6 in pubertal children), the highest final height gain was achieved in those treated for at least 2 years prepuberty (1.32±.5 SDS). Factors associated with greater adult height gain were: (a) less height, weight and BMI at start of treatment, (b) lower chronological and bone age with lower IGF-I before treatment, (c) greater distance to target height, (d) higher growth velocity the first and second year of treatment, and higher height gain before and during puberty. The percentage of patients with good response in the first year ranged from 46.6% to 81.6% depending on the criteria. Growth velocity increase ≥3cm/first year correlated best with long-term response. ConclusionrhGH treatment in children born SGA produced a varying increase in adult height that allowed them to reach their adult height. The best results occurred in the prepubertal group and did not depend on pituitary GH response.

Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose.

The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.

PSXIII-31 Hypothalamic and pituitary responses to resistin in sheep: integration of resistin and leptin signaling involving SOCS-3 and LepRb

Abstract Leptin and resistin play important roles in regulating body weight and glucose metabolism. Herein, we hypothesized that resistin is a factor leading to decreased tissue sensitivity to leptin through effects on SOCS-3 and LeptRb expression. Expression of SOCS-3 and LeptRb were determined using Real-Time PCR in selected brain tissues: arcuate nucleus (ARC), ventro- and dorsomedial nuclei (VMH/DMH), preoptic area (POA) and anterior pituitary (AP). Thirty ewes (10/group), ovariectomized with E2-replacement, were fed ad libitum and housed under natural photoperiod. Intravenous treatments consisted of 1) control, 2) low dose of rbresistin (R1; 1.0 μg/kg BW), and 3) high dose of rbresistin (R2; 10.0 μg/kg BW). During long days (LD), LeptRb transcript in ARC decreased in response to R2 (P &amp;lt; 0.001) compared to Control. Expression of LeptRb in VMH/DMH decreased in response to R1(P &amp;lt; 0.001) and R2 (P &amp;lt; 0.001) during short days (SD) and to R2 (P &amp;lt; 0.001) during LD. Conversely, LeptrB transcript increased (P &amp;lt; 0.001) 8-fold in R1 and 4-fold in R2 (P &amp;lt; 0.05) in POA during SD. LeptrB transcript in the AP increased (P &amp;lt; 0.001) 2.1- and 1.8-fold, respectively, in response to R1 and R2 during LD. Within the ARC, SOCS-3 expression increased (P &amp;lt; 0.001) after R2 in LD. In POA, a 2.3-fold (P &amp;lt; 0.001) increase was noted in R2 only during LD. Moreover, SOCS-3 transcript increased in the AP during both LD (8.5-fold) and SD (5.8-fold) in response to R2 (P &amp;lt; 0.001). Evidence indicates that resistin resulted in a consistent decrease in LeptRb (except POA) and increase in SOCS-3 expression during LD in all hypothalamic nuclei. In AP, resistin increased SOCS-3 during both LD and SD and LeptRb transcript during LD. Taken together, the effects of resistin appear to be strongly associated with photoperiod-driven changes in the leptin signaling pathway, which may underlie the phenomenon of leptin resistance.

Insulin-induced hypoglycaemia suppresses pulsatile luteinising hormone secretion and arcuate Kiss1 cell activation in female mice.

Stress suppresses pulsatile luteinising hormone (LH) secretion in a variety of species, although the mechanism underlying this inhibition of reproductive function remains unclear. Metabolic stress, particularly hypoglycaemia, is a clinically-relevant stress type that is modelled with bolus insulin injection (insulin-induced hypoglycaemia). The present study utilised ovariectomised C57BL/6 mice to test the hypothesis that acute hypoglycaemia suppresses pulsatile LH secretion via central mechanisms. Pulsatile LH secretion was measured in 90-minute sampling periods immediately prior to and following i.p. injection of saline or insulin. The secretion of LH was not altered over time in fed animals or acutely fasted (5hours) animals following an i.p. saline injection. By contrast, insulin elicited a robust suppression of pulsatile LH secretion in fasted animals, preventing LH pulses in five of six mice. To identify the neuroendocrine site of impairment, a kisspeptin challenge was performed in saline or insulin pre-treated animals in a cross-over design. LH secretion in response to exogenous kisspeptin was not different between animals pre-treated with saline or insulin, indicating normal gonadotrophin-releasing hormone cell and pituitary responses during acute hypoglycaemia. Based on this finding, the effect of insulin-induced hypoglycaemia on arcuate kisspeptin (Kiss1) cell function was determined using c-Fos as a marker of neuronal activation. Insulin caused a significant suppression in the percentage of Kiss1 cells in the arcuate nucleus that contained c-Fos compared to saline-injected controls. Taken together, these data support the hypothesis that insulin-induced hypoglycaemia suppresses pulsatile LH secretion in the female mouse via predominantly central mechanisms, which culminates in the suppression of the arcuate Kiss1 population.

Modulation of Pituitary Response by Dietary Lipids and Throughout a Temperature Fluctuation Challenge in Gilthead Sea Bream

Low temperatures provoke drastic reductions in gilthead sea bream (Sparus aurata) activity and nourishment, leading to growth arrest and a halt in production. However, scarce data exist concerning the implications of central core control during the cold season. The aim of this work was to study the effects of low temperature and recovery from such exposure on the pituitary activity of sea bream juveniles fed 18% or 14% dietary lipid. A controlled indoor trial was performed to simulate natural temperature fluctuation (22 °C to 14 °C to 22 °C). Meanwhile, we determined the regulatory role of the pituitary by analyzing the gene expression of some pituitary hormones and hormone receptors via qPCR, as well as plasma levels of thyroidal hormones. In response to higher dietary lipids, hormone pituitary expressions were up-regulated. Induced low temperatures and lower ingesta modulated pituitary function up-regulating GH and TSH and thyroid and glucocorticoid receptors. All these findings demonstrate the capacity of the pituitary to recognize both external conditions and to modulate its response accordingly. However, growth, peripheral tissues and metabolism were not linked or connected to pituitary function at low temperatures, which opens an interesting field of study to interpret the hypothalamus–pituitary–target axis during temperature fluctuations in fish.

Reduction of acute mild stress corticosterone response and changes in stress-responsive gene expression in male Balb/c mice after repeated administration of a Rhodiola rosea L. root extract.

Rhodiola rosea L. (R. rosea) is an adaptogenic plant increasing body resistance to stress. Its efficacy has been evidenced mainly in chronic stress models, data concerning its effect in acute stress and underlying mechanisms being scarce. The objective was to investigate the effect of repeated doses of a R. rosea hydroethanolic root extract (HRE) on hypothalamic pituitary adrenal response in a murine model of acute mild stress and also the mechanisms involved. Stress response was measured in Balb/c mice having received by gavage HRE (5 g/kg) or vehicle daily for 2 weeks before being submitted to an acute mild stress protocol (open‐field test then elevated plus maze). Corticosterone was measured in plasma from mandibular vein blood drawn before and 30, 60, and 90 min after initiation of the stress protocol. Mice were sacrificed at 90 min, and the hippocampus, prefrontal cortex, and amygdala were excised for high‐frequency RT‐PCR gene expression analysis. At 30 min after acute mild stress induction, corticosterone level in mice having received the HRE was lower than in control mice and comparable to that in nonstressed mice in the HRE group. HRE administration induced brain structure‐dependent changes in expression of several stress‐responsive genes implicated in neuronal structure, HPA axis activation, and circadian rhythm. In the acute mild stress model used, R. rosea HRE decreased corticosterone level and increased expression of stress‐responsive genes, especially in the hippocampus and prefrontal cortex. These findings suggest that R. rosea HRE could be of value for modulating reactivity to acute mild stress.

Lame cows have a subdued hypothalamus-pituitary axis as revealed by LH release in response to exogenous endocrine challenges

Lameness is a serious concern in cows due to its multilevel effects and increasing incidences. The ability of anterior pituitary and hypothalamus to release LH, a prime reproductive hormone, is unknown in lame cows. Our study tested this ability by exogenous endocrine challenge using Buserelin acetate (GnRH analogue) and estradiol valerate (EV). The study included moderately lame (L; n=7) either cyclic (LC; n=3) or anestrus (LA; n=4); and normal cyclic, non–lame (NL; n=5) cows. Progesterone blocks LH release, so it was lowered by injecting PG in cyclic cows. After 14 h, all cows were given a walk for 5 min and immediately thereafter injected with 0.008 mg GnRH and 4 h later with 1 mg of EV. Blood plasma progesterone, cortisol and LH were quantified, periodically. There was a significant delay in the onset (105.0 vs 75.0±7.0 vs 54.0±9.0 min) and duration (22.5±5.3 vs 80.0±10.8 vs 117.0±2.7 min) of LH surge in LA vs LC vs NL cows; the surge was absent in two LA cows. The altered LH profile was attributed to a 3 fold (in L) vs 1.6 fold (in NL) rise in cortisol. LH released (ng/ml) in response to EV was also low in LA (31.5±2.4) and LC (69.9±7.2) than NL (79.2±7.0) cows. In conclusion, lame cows subjected to walk exhibited reduced pituitary response to release LH following exogenous GnRH as also a reduced ability of hypothalamus to stimulate LH release in response to exogenous estradiol.

The Pituitary Transcriptional Response Related to Feed Conversion in Pigs.

Over the decades, pig breeding objectives have focused on improving the meat content in the carcass without taking into consideration the more effective fattening indicators that affect feed conversion. At present, pig growth traits associated particularly with animal feeding have become crucial due to their economic significance. This is especially evident in countries where pigs are maintained on large farms. The present study indicates that pituitary differentially expressed genes (DEGs) are activated in response to variable feed conversion (FC) in pigs. The experiment included two native Polish breeds: Puławska and Złotnicka White (ZW). The whole pituitary transcriptome was sequenced using next-generation sequencing (NGS) technology. The RNA-seq method identified over 500 and 300 DEGs in the pituitaries of the ZW and the Puławska pig populations, respectively, that were associated with hormonal regulation, notch signaling, and Wnt pathways. Lower FC in the ZW pigs favoured increased fat content in the body and significantly higher prolactin expression. The obtained results indicate that low FC values in pigs are related to slower growth or increased fat content, which suggests various pituitary responses. Therefore, the identified candidate genes were not directly associated with feed conversion values but with other factors. However, the present study delivers new insights into pituitary regulation in pigs.

Hypothalamic-Pituitary and Adipose Tissue Responses to the Effect of Resistin in Sheep: The Integration of Leptin and Resistin Signaling Involving a Suppressor of Cytokine Signaling 3 and the Long Form of the Leptin Receptor.

We hypothesized that resistin is engaged in the development of leptin central insensitivity/resistance in sheep, which is a unique animal model to explore reversible leptin resistance. Thirty Polish Longwool ewes, which were ovariectomized with estrogen replacement, were used. Treatments consisted of the intravenous injection of control (saline) or recombinant bovine resistin (rbresistin): control (Control; n = 10), a low dose of rbresistin (R1; 1.0 μg/kg body weight (BW); n = 10), and a high dose of rbresistin (R2; 10.0 μg/kg BW; n = 10). The studies were performed during short-day (SD) and long-day (LD) photoperiods. Leptin and resistin concentrations were determined. Expression levels of a suppressor of cytokine signaling (SOCS)-3 and the long form of the leptin receptor (LeptRb) were determined in selected brain regions, including in the anterior pituitary (AP), hypothalamic arcuate nucleus (ARC), preoptic area (POA), and ventro- and dorsomedial nuclei (VMH/DMH). The results indicate that resistin induced a consistent decrease in LeptRb (except in POA) and an increase in SOCS-3 expression during the LD photoperiod in all selected brain regions. In conclusion, the results demonstrate that the action of resistin appears to be strongly associated with photoperiod-driven changes in the leptin signaling pathway, which may underlie the phenomenon of central leptin resistance.

Gonadotrope androgen receptor mediates pituitary responsiveness to hormones and androgen-induced subfertility

Many women with hyperandrogenemia suffer from irregular menses and infertility. However, it is unknown whether androgens directly affect reproduction. Since animal models of hyperandrogenemia-induced infertility are associated with obesity, which may impact reproductive function, we have created a lean mouse model of elevated androgen using implantation of low dose dihydrotestosterone (DHT) pellets to separate the effects of elevated androgen from obesity. The hypothalamic-pituitary-gonadal axis controls reproduction. While we have demonstrated that androgen impairs ovarian function, androgen could also disrupt neuroendocrine function at the level of brain and/or pituitary to cause infertility. To understand how elevated androgens might act on pituitary gonadotropes to influence reproductive function, female mice with disruption of the androgen receptor (Ar) gene specifically in pituitary gonadotropes (PitARKO) were produced. DHT treated control mice with intact pituitary Ar (Con-DHT) exhibit disrupted estrous cyclicity and fertility with reduced pituitary responsiveness to GnRH at the level of both calcium signaling and LH secretion. These effects were ameliorated in DHT treated PitARKO mice. Calcium signaling controls GnRH regulation of LH vesicle exotocysis. Our data implicated upregulation of GEM (a voltage-dependent calcium channel inhibitor) in the pituitary as a potential mechanism for androgen's pathological effects. These results demonstrate that gonadotrope AR, as an extra-ovarian regulator, plays an important role in reproductive pathophysiology.