Socioeconomic status and risk of osteoporotic fractures and the use of DXA scans: data from the Danish population-based ROSE study.

There is a need of studies exploring the link between socioeconomic status and DXA scans and osteoporotic fracture, which was the aim of the present study. No differences in socioeconomic status and risk of osteoporotic fractures were found. However, women with further/higher education and higher income are more often DXA-scanned. INTRODUCTION: Lower socioeconomic status is known to be associated with a range of chronic conditions and with access to health care services. The link between socioeconomic status and the use of DXA scans and osteoporotic fracture, however, needs to be explored more closely. Therefore, the aim of this study was to examine the relationship between socioeconomic status and both DXA scan utilization and major osteoporotic fractures (MOF) using a population-based cohort of Danish women and national registers. METHODS: The study included 17,155 women (65-81 years) sampled from the Risk-stratified Osteoporosis Strategy Evaluation study (ROSE). Information on socioeconomic background, DXA scans, and MOFs was retrieved from national registers. Competing-risk regression analyses were performed. Mean follow-up was 4.8 years. RESULTS: A total of 4245 women had a DXA scan (24.7%) and 1719 (10.0%) had an incident MOF during follow-up. Analyses showed that women with basic education had a lower probability of undergoing DXA scans than women with further or higher education (greater than upper secondary education and vocational training education) (subhazard ratio (SHR) = 0.82; 95% CI 0.75-0.89, adjusted for age and comorbidity). Moreover, women with disposable income in the low and medium tertiles had a lower probability of undergoing DXA scans than women in the high-income tertile (SHR = 0.90; 95% CI 0.84-0.97 and SHR = 0.88, 95% CI 0.82-0.95, respectively, adjusted for age and comorbidity). No association between socioeconomic background and probability of DXA was found in adjusted analyses. CONCLUSION: The study found no differences in risk of osteoporotic fractures depending on socioeconomic status. However, women with further or higher education as well as higher income are more often DXA-scanned.

The effect of melatonin from slow-release implants on basic and TLR-4-mediated gene expression of inflammatory cytokines and their receptors in the choroid plexus in ewes.

The present study concerns the effect of melatonin from slow-release implants on the expression of genes coding interleukin-1ß (Il1B), inerleukin-6 (Il6), tumour necrosis factor α (Tnf) and their receptors: IL-1 receptor type I (Il1r1) and type II (Il1r2), IL-6 receptor (Il6r) and signal transducer (Il6st), TNFα receptor type I (Tnfrsf1a) and II (Tnfrsf1b) and retinoid-related orphan receptor α (RorA) and Rev.-erbα in the ovine choroid plexus (CP) under basal and lipopolysaccharide (LPS)-challenged conditions. Studies were performed on four groups: 1) sham-implanted and placebo-treated, 2) melatonin-implanted (Melovine, 18mg) and placebo-treated, 3) sham-implanted and LPS-treated (400ng/kg of body weight) and 4) melatonin-implanted and LPS-treated. Under basal conditions, we observed weak expression of Tnf, low expression of Il1B, Il6 and Il1r2 and intermediate expression of other cytokines receptors. LPS treatment induced (P≤0.05) expression in all cytokines and their receptors, except Il6r 3h after the administration. Melatonin attenuated (P≤0.05) LPS-induced up-regulation of Il6 but had no effect on other cytokines and their receptors and up-regulated (P≤0.05) Rev.-erbα expression under basal conditions. This indicates that melatonin from slow-release implants suppresses TLR4-mediated Il6 expression in the ovine CP via a mechanism likely involving clock genes.

Influence of preterm delivery on ghrelin and obestatin concentrations in maternal plasm, milk and their expression in mammary epithelial cells.

Ghrelin and obestatin are gastrointestinal peptides with a potential role in the programming of metabolism in newborns. The present study aimed to investigate the influence of preterm delivery on ghrelin and obestatin concentrations in the maternal blood plasma and breast milk as well as their gene expressions in the mammary epithelial cells (MECs). On the 3rd day after delivery, milk and plasma samples were collected from mothers that carried to term or gave birth prematurely (< 36 weeks of gestation) and analyzed for ghrelin and obestatin concentrations. MECs isolated from the milk were analyzed for the relative expression of GHRL splice variants. In both groups ghrelin concentrations were significantly lower in milk than in blood plasma. In the preterm group obestatin concentrations were significantly higher in milk than in blood plasma but significantly lower in comparison to that of the control mothers. The expression of GHRL mRNAs was higher (P < 0.05) in MECs isolated from the preterm group as compared to those isolated from control mothers. The concentration of obestatin (but not ghrelin) in the breast milk is dependent on the term of pregnancy. Moreover, the lactating mammary gland is one of the sources of ghrelin and obestatin.

Central Interleukin-1ß Suppresses the Nocturnal Secretion of Melatonin.

In vertebrates, numerous processes occur in a rhythmic manner. The hormonal signal reliably reflecting the environmental light conditions is melatonin. Nocturnal melatonin secretion patterns could be disturbed in pathophysiological states, including inflammation, Alzheimer's disease, and depression. All of these states share common elements in their aetiology, including the overexpression of interleukin- (IL-) 1ß in the central nervous system. Therefore, the present study was designed to determine the effect of the central injection of exogenous IL-1ß on melatonin release and on the expression of the enzymes of the melatonin biosynthetic pathway in the pineal gland of ewe. It was found that intracerebroventricular injections of IL-1ß (50 µg/animal) suppressed (P < 0.05) nocturnal melatonin secretion in sheep regardless of the photoperiod. This may have resulted from decreased (P < 0.05) synthesis of the melatonin intermediate serotonin, which may have resulted, at least partially, from a reduced expression of tryptophan hydroxylase. IL-1ß also inhibited (P < 0.05) the expression of the melatonin rhythm enzyme arylalkylamine-N-acetyltransferase and hydroxyindole-O-methyltransferase. However, the ability of IL-1ß to affect the expression of these enzymes was dependent upon the photoperiod. Our study may shed new light on the role of central IL-1ß in the aetiology of disruptions in melatonin secretion.

Interleukin-1 ß Modulates Melatonin Secretion in Ovine Pineal Gland: Ex Vivo Study.

The study was designed to determine the effect of proinflammatory cytokine, interleukin- (IL-) 1ß, on melatonin release and expression enzymes essential for this hormone synthesis: arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) in ovine pineal gland, taking into account the immune status of animals before sacrificing. Ewes were injected by lipopolysaccharide (LPS; 400 ng/kg) or saline, two hours after sunset during short day period (December). Animals were euthanized three hours after the injection. Next, the pineal glands were collected and divided into four explants. The explants were incubated with (1) medium 199 (control explants), (2) norepinephrine (NE; 10 µM), (3) IL-1ß (75 pg/mL), or (4) NE + IL-1ß. It was found that IL-1ß abolished (P < 0.05) NE-induced increase in melatonin release. Treatment with IL-1ß also reduced (P < 0.05) expression of AA-NAT enzyme compared to NE-treated explants. There was no effect of NE or IL-1ß treatment on gene expression of HIOMT; however, the pineal fragments isolated from LPS-treated animals were characterized by elevated (P < 0.05) expression of HIOMT mRNA and protein compared to the explants from saline-treated ewes. Our study proves that IL-1ß suppresses melatonin secretion and its action seems to be targeted on the reduction of pineal AA-NAT protein expression.

Salsolinol: a potential modulator of the activity of the hypothalamic-pituitary-adrenal axis in nursing and postweaning sheep.

The most well-known physiological action of salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is the stimulation of prolactin secretion, especially during lactation. In addition, our recent work demonstrated that salsolinol inhibits the stress-induced activity of the hypothalamic-pituitary-adrenal (HPA) axis in lactating sheep. Here, we investigated whether salsolinol regulates the basal activity of the HPA axis in lactating sheep and whether its inhibitory action on the stress-induced activity of the HPA axis is present during the postweaning period. The first experiment was performed during the fifth week of lactation, in which unstressed sheep received an intracerebroventricular infusion of an antagonistic analogue of salsolinol, 1-MeDIQ (1-methyl-3,4-dihydroisoquinoline). Simultaneously, the infundibular nucleus and/or median eminence was perfused using the push-pull method. Sheep that received 1-MeDIQ infusion showed significantly higher concentration of plasma ACTH during the second, third, and fourth hour (P < 0.001, P < 0.01, and P < 0.001, respectively) and cortisol during the third and fourth hour (P < 0.001 and P < 0.01, respectively) than did sheep that received control infusion. There was no significant difference in the mean perfusate corticotropin-releasing hormone concentration between the 1-MeDIQ and control treatments. In the second experiment, sheep received an intracerebroventricular infusion of salsolinol during the ninth week of lactation and 48 h after lamb weaning. A comparison between the control groups in the first and second experiments revealed that sheep after weaning (ninth week of lactation) had significantly higher mean ACTH (P < 0.001) and cortisol (P < 0.001) concentrations during the first 2 h of the experiment than the nursing females (fifth week of lactation) had. Salsolinol significantly reduced the increased concentrations of ACTH and cortisol (P < 0.01) in sheep after lamb weaning. However, there was no difference in the expression of proopiomelanocortin messenger RNA within the anterior pituitary between the control and salsolinol-treated groups. In conclusion, salsolinol regulates the basal activity of the HPA axis in lactating sheep. In addition, the HPA axis of postweaning females is more sensitive to stressors associated with the experimental procedures, and salsolinol attenuates ACTH and cortisol release in this phenomenon.

Time-dependent supplementation of vitamin E influences leptin expression in the aortic layers of rats fed atherogenic diet.

An excessive consumption of a diet rich in saturated fatty acids is a key factor in pathogenesis of cardiovascular diseases which are strictly connected with leptin imbalance in the vessels. However, whether vitamin E supplementation would influence leptin expression in aortic layers is still unknown. For 3 or 6 weeks male Wistar rats were fed a high-fat (20% w/w) diet with lard as dietary fat source with or without vitamin E supplementation (50 mg/100 g of diet). The 6-week intake of an atherogenic diet increased total cholesterol (TC) and high density lipoprotein cholesterol (HDL) plasma levels simultaneously lowering TC/HDL ratio (ANOVA p≤0.0001 for all three parameters). After longer period of feeding it was stated that leptin expression in all three aortic layers was enhanced (ANOVA p≤0.0001 for endothelium, tunica media and adventitia, respectively) with decreased leptin plasma concentration (ANOVA p≤0.0001). After both periods of feeding vitamin E supplementation caused an increase in plasma HDL content and a decrease of TC/HDL ratio. In the 3-week experiment vitamin E addition caused a decrease in leptin plasma levels (Fisher's test, 3L versus 3LE: p≤0.002) and an increase in leptin expression in all three aortic layers (Fisher's test, 3L versus 3LE p≤0.005, p≤0.01 and p≤0.05 respectively for endothelium, tunica media and adventitia). The contradictory results were observed in the 6-week experiment in which vitamin supplementation decreased leptin expression in the aortic endothelium (Fisher's test, 6L versus 6LE: p≤0.001) with lack of changes in the other two layers of the aorta and plasma. The study showed that vitamin E supplementation influenced leptin expression in aortic layers in rats fed atherogenic diet differently depending on the length of feeding period. It may suggest that vitamin E consumption plays an important role in the control of leptin status in the endothelium.

A functional amino acid substitution in the glucose-dependent insulinotropic polypeptide receptor (GIPR) gene is associated with lower bone mineral density and increased fracture risk.

CONTEXT: Food ingestion decreases bone resorption, and glucose-dependent insulinotropic polypeptide (GIP) may mediate this effect. Mice overexpressing GIP have increased osteoblast activity and are rescued from age-related bone loss, whereas GIPR knockout mice have decreased cortical bone mass and compromised bone quality. Carriers of the functional variant GIPR Glu354Gln (rs1800437) have higher plasma glucose 2 hours after glucose ingestion, suggesting that the variant encoding GIPR 354Gln decreases the effect of GIP. OBJECTIVE: The objective of the study was to investigate the effect of GIPR Glu354Gln on bone mineral density (BMD) and fracture risk. DESIGN: This was a prospective, comprehensive, cohort study (number NCT00252408). PARTICIPANTS: A total of 1686 perimenopausal women were included. MAIN OUTCOME MEASURES: Dual-energy X-ray absorptiometry was performed at baseline and after 10 years. Incident fractures were recorded during the follow-up and were obtained from the Danish National Patient Registry, giving a total follow-up time of a minimum 16 years. RESULTS: After 10 years, women with the minor frequency C allele of rs1800437 (354Gln) had significantly lower BMD at the femoral neck compared with carriers of the major G-allele (CC: 0.755 ± 0.015 g/cm(2) vs CG: 747 ± 0.005 g/cm(2); GG: 0.766 ± 0.004 g/cm(2), P < .001). Correspondingly, total hip BMD was significantly lower among C allele carriers (CC: 0.881 ± 0.016 g/cm(2); CG: 0.884 ± 0.005 g/cm(2); and GG: 0.906 ± 0.004 g/cm(2), P < .001). Finally, women homozygous for the variant C allele had an increased risk (hazard ratio 1.6, confidence interval 1.0-2.6, P < .05) of nonvertebral fractures. CONCLUSION: This study demonstrates an association between a functional GIPR polymorphism Glu354Gln (rs1800437) and BMD and fracture risk. These findings further establish GIP to be involved in the regulation of bone density.

Influence of fundectomy and intraperitoneal or intragastric administration of apelin on apoptosis, mitosis, and DNA repair enzyme OGG1,2 expression in adult rats gastrointestinal tract and pancreas.

Apelin, endogenous ligand of G protein-coupled apelin receptor (APJ), is released into the gastrointestinal lumen, however, local effect of luminal apelin on gut epithelium has not been elucidated so far. The present study aimed to determine the effects of fundectomy, and intraperitoneal or intragastric administration of apelin on pancreatic, gastric and intestinal epithelium apoptosis, mitosis and DNA repair enzyme OGG1,2 expression in adult Wistar rats. Apelin-13 was given by intraperitoneal or gastric gavage twice a day for 10 days (100 nmol/kg b. wt./day). Fundectomized rats did not receive apelin. Control groups received saline as placebo. At the end of the experiment the rats were sacrificed and the pancreas, gastric fundus, duodenum, middle jejunum and colon tissue samples were harvested for immunofluorescence studies. Intraperitoneal and intragastric apelin-13 reduced apoptosis, mitosis and number of DNA damages in rats gastrointestinal tract (p≤0.001) as compared to control. In fundectomized rats, the apoptotic index in the pancreas and colon was decreased (p<0.001), and in the stomach and jejunum was increased (p<0.001). Mitotic index was decreased in all gastrointestinal tissues. Number of DNA damages (p≤0.001) in fundectomized rats was reduced except stomach where OGG1,2 expression was increased (p≤0.001) as compared to control. In conclusion, circulating and luminal exogenous apelin-13 caused similar effects on intestinal epithelium. Endogenous (gastric) apelin is important for renewal of intestinal epithelium in adult rats. Pharmacological doses of apelin-13 may reduce the cell turnover in the upper gastrointestinal tract epithelium and pancreas, and improve the overall gut health.

The effect of rivastigmine on the LPS-induced suppression of GnRH/LH secretion during the follicular phase of the estrous cycle in ewes.

This study was designed to determine the effect of a potent subcutaneously injected acetylcholinesterase inhibitor, rivastigmine (6mg/animal), on the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release during inflammation induced by an intravenous lipopolysaccharide (LPS) (400ng/kg) injection in ewes during the follicular phase of the estrous cycle. The results are expressed as the mean values from -2 to -0.5h before and +1 to +3h after treatment. Rivastigmine decreased the acetylcholinesterase concentration in the blood plasma from 176.9±9.5 to 99.3±15.1µmol/min/ml. Endotoxin suppressed LH (5.4±0.6ng/ml) and GnRH (4.6±0.4pg/ml) release; however, the rivastigmine injection restored the LH concentration (7.8±0.8ng/ml) to the control value (7.8±0.7ng/ml) and stimulated GnRH release (7.6±0.8pg/ml) compared to the control (5.9±0.4pg/ml). Immune stress decreased expression of the GnRH gene and its receptor (GnRH-R) in the median eminence as well as LHß and GnRH-R in the pituitary. In the case of the GnRH and LHß genes, the suppressive effect of inflammation was negated by rivastigmine. LPS stimulated cortisol and prolactin release (71.1±14.7 and 217.1±8.0ng/ml) compared to the control group (9.0±5.4 and 21.3±3.5ng/ml). Rivastigmine also showed a moderating effect on cortisol and prolactin secretion (43.1±13.1 and 169.7±29.5ng/ml). The present study shows that LPS-induced decreases in GnRH and LH can be reduced by the AChE inhibitor. This action of the AChE inhibitor could result from the suppression of pro-inflammatory cytokine release and the attenuation of the stress response. However, a direct stimulatory effect of ACh on GnRH/LH secretion should also be considered.

Inhibition of acetylcholinesterase activity by rivastigmine decreases lipopolysaccharide-induced IL-1ß expression in the hypothalamus of ewes.

The present study was designed to determine the effect of subcutaneous rivastigmine treatment on IL-1ß expression and IL-1 type I receptor (IL-1R1) gene expression in the hypothalamic structures (preoptic area [POA], anterior hypothalamus [AHA], and medial basal hypothalamus [MBH]) of ewes after lipopolysaccharide (LPS) treatment. Endotoxin treatment increased (P ≤ 0.01) both IL-1ß and IL-1R1 gene expression in the POA, AHA, and MBH compared with the control group, whereas concomitant rivastigmine and LPS injection abolished this stimulatory effect. It was also found that LPS elevated (P ≤ 0.01) IL-1ß concentration in the hypothalamus (71.0 ± 2.3 pg/mg) compared with controls (16.1 ± 3.6 pg/mg). The simultaneous injection of LPS and rivastigmine did not increase IL-1ß concentration in the hypothalamus (24.6 ± 13.0 pg/mg). This central change in IL-1ß synthesis seems to be an effect of acetylcholinesterase (AChE) inhibition by rivastigmine, which decreases (P ≤ 0.01) the activity of this enzyme from 78.5 ± 15.0 µmol · min(-1) · g(-1) of total protein in the control and 68.8 ± 9.8 µmol · min(-1) · g(-1) of total protein in LPS-treated animals to 45.2 ± 5.6 µmol · min(-1) · g(-1) of total protein in the rivastigmine and LPS-treated group. Our study showed that rivastigmine could effectively reverse the stimulatory effect of immune stress induced by LPS injection on IL-1ß synthesis through a decrease in AChE activity in the hypothalamic area of sheep. Our results also proved that the cholinergic anti-inflammatory pathway could directly modulate the central response to endotoxin.

[Effect of cinnamon and lavender oils on FtsZ gene expression in the Staphylococus aureus ATCC 29213].

This study was designed to determine the effect of lavender and cinnamon oils on FtsZ gene expression in Staphylococcus aureus ATCC 29213. The cinnamon and lavender oils at least partially results from the inhibition of FtsZ transcription and disruption of cell division process at the level of the septum synthesis, what is similar to mechanisms of drug action used in anti-staphylococcal therapies. The presented results could be an important background for the further detailed research, which is needed to clarify the effect of essential oils on FtsZ synthesis at the posttranscriptional level and other stages of cell division process of S. aureus and other pathogenic bacteria.

Caffeine's mechanisms of action and its cosmetic use.

Caffeine is being increasingly used in cosmetics due to its high biological activity and ability to penetrate the skin barrier. This alkaloid is frequently used as a hydrophilic model substance in human and animal skin penetration as well as different synthetic membrane using Franz diffusion cell experiments. The commercially available topical formulations of caffeine normally contain 3% caffeine. As for a cosmetic purpose, caffeine is used as an active compound in anti-cellulite products because it prevents excessive accumulation of fat in cells. This alkaloid stimulates the degradation of fats during lipolysis through inhibition of the phosphodiesterase activity. Caffeine has potent antioxidant properties. It helps protect cells against the UV radiation and slows down the process of photoaging of the skin. Moreover, caffeine contained in cosmetics increases the microcirculation of blood in the skin and also stimulates the growth of hair through inhibition of the 5-α-reductase activity.

Central injection of exogenous IL-1ß in the control activities of hypothalamic-pituitary-gonadal axis in anestrous ewes.

This study was performed to determine the effect of intracerebroventricular (icv) injection of interleukin (IL)-1ß on the gene expression, translation and release of gonadotropin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) gene expression in the hypothalamus of anestrous ewes. In the anterior pituitary gland (AP), the expression of genes encoding: GnRHR, ß subunits of luteinizing hormone (LH) and folliculotropic hormone (FSH) was determined as well as the effect of IL-1ß on pituitary gonadotropins release. The relative mRNA level was determined by real-time PCR, GnRH concentration in the cerebrospinal fluid (CSF) was assayed by ELISA and the plasma concentration of LH and FSH were determined by radioimmunoassay. Our results showed that icv injection of IL-1ß (10 or 50 µg/animal) decreased the GnRH mRNA level in the pre-optic area (POA) (35% and 40% respectively; p ≤ 0.01) and median eminence (ME) (75% and 70% respectively; p ≤ 0.01) and GnRHR gene expression in ME (55% and 50% respectively; p ≤ 0.01). A significant decrease in GnRHR mRNA level in the AP in the group treated with the 50 µg (60%; p ≤ 0.01) but not with the 10 µg dose was observed. The centrally administrated IL-1ß lowered also GnRH concentration in the CSF (60%; p ≤ 0.01) and reduced the intensity of GnRH translation in the POA (p ≤ 0.01). It was not found any effect of icv IL-1ß injection upon the release of LH and FSH. However, the central injection of IL-1ß strongly decreased the LHß mRNA level (41% and 50%; p ≤ 0.01; respectively) and FSHß mRNA in the case of the 50 µg dose (49%; p ≤ 0.01) in the pituitary of anestrous ewes. These results demonstrate that the central IL-1ß is an important modulator of the GnRH biosynthesis and release during immune/inflammatory challenge.

Expression of interleukin (IL)-1ß and IL-1 receptors genes in the hypothalamus of anoestrous ewes after lipopolysaccharide treatment.

This study was designed to determine the effect of intravenous lipopolysaccharide (LPS) administration on the secretion of interleukin (IL)-1ß and IL-1 receptors (IL-1Rs) gene expression in the hypothalamus of anoestrous ewes. Gene expression of IL-1ß and its receptors was assayed by the real-time polymerase chain reaction. The expression of IL-1ß in the hypothalamus was detected using Western blot. Our results showed that IL-1ß mRNA is transcribed in the ovine hypothalamus. Lipopolysaccharide increased (p ≤ 0.01) the IL-1ß gene expression in the pre-optic area 2.4-fold, the anterior hypothalamus (AHA) 3.4-fold, the medial basal hypothalamus 3.7-fold and the medial eminence 3.9-fold. The pro-form and mature form of IL-1ß protein were found in the hypothalamus after endotoxin injection. In general, the endotoxin also increased more than two times (p ≤ 0.01) the expression of IL-1 receptor type I (IL-1R1) and type II (IL-1R2) genes in the hypothalamus, except the AHA, where the number of IL-1R2 mRNA was extremely low and not sufficient to the quantitative analysis. These results demonstrate that the peripheral immune/inflammatory challenge increases the IL-1ß expression in the hypothalamus. This endogenous IL-1ß seems to be involved in the modulation of processes which are regulated at the hypothalamic level. One of these processes could be a reproduction.

Effect of LPS on reproductive system at the level of the pituitary of anestrous ewes.

In our research we focused our attention on the effect of the immune stress induced by bacterial endotoxin-lipopolysaccharide (LPS) on the hypothalamic-pituitary-gonadal axis (HPG) at the pituitary level. We examined the effect of intravenous (i.v.) LPS injection on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from the anterior pituitary gland (AP) in anestrous ewes. The effect of endotoxin on prolactin and cortisol circulating levels was also determined. We also researched the effect of immune challenge on the previously mentioned pituitary hormones and their receptors genes expression in the AP. Our results demonstrate that i.v. LPS injection decreased the plasma concentration of LH (23%; p < 0.05) and stimulates cortisol (245%; p < 0.05) and prolactin (60%; p < 0.05) release but has no significant effect on the FSH release assayed during 6 h after LPS treatment in comparison with the control levels. The LPS administration affected the genes expression of gonadotropins' ß-subunits, prolactin and their receptors in the AP. Endotoxin injection significantly decreased the LHß and LH receptor (LHR) gene expression (60%, 64%; p < 0.01 respectively), increased the amount of mRNA encoding FSHß, FSH receptor (FSHR) (124%, 0.05; 166%, p < 0.01; respectively), prolactin and prolactin receptor (PRLR) (50%, 47%, p < 0.01; respectively). The presented, results suggest that immune stress is a powerful modulator of the HPG axis at the pituitary level. The changes in LH secretion could be an effect of the processes occurring in the hypothalamus. However, the direct effect of immune mediators, prolactin, cortisol and other components of the hypothalamic pituitary-adrenal (HPA) axis on the activity of gonadotropes has to be considered as well. Those molecules could affect LH synthesis directly through a modulation at all stages of LHß secretion as well as indirectly influencing the GnRHR expression and leading to reduced pituitary responsiveness to GnRH stimulation.