Local Hormone Production Research Articles

A Functionally Conserved Regulatory Module Confers Universal Regeneration Potential to Plant Tissues in Response to Injury

Plants can repair wounds throughout their body when they suffer injuries. The molecular mechanisms underlying this universal regeneration potential, and how regulation of tissue regeneration compares with its formation during development, remains unknown. Here, we reveal an essential role for members of the PLETHORA(PLT)/ AINTEGUMENTA(ANT) gene family in activating innate responses to injuries of the form that growing aerial parts of the plant naturally encounter. Strikingly, PLT act through the embryonic symmetry determinant CUP-SHAPED COTYLEDON2(CUC2) but not through root or shoot stem cell regulators in this process. Wound repair and vascular regeneration in damaged aerial organs growing in a normal developmental context were severely impaired in plt/ant mutant combinations as well as in cuc2 mutant. We find that the PLT-CUC2 module-dependent control of local hormonal environment and cell polarisation drives vascular regeneration in damaged aerial organs. We further provide several lines of evidence for PLT-CUC2 driven mechanism of wound repair and finally, rescue the regeneration defects by reconstituting endogenous local hormone production in the mutants. Interestingly, the necessity of PLT-CUC2 module specifically for vascular regeneration, but not vascular tissue development, distinguishes tissue’s ability to repair wound from its developmental program. This study reveals the essential mechanism of wound repair across the plant body and discerns the regulation of tissue regeneration from its formation during development.

LEVEL OF HORMONES IN ENDOMETRIAL CANCER TISSUE AND INTACT OVARIES ASSOCIATED WITH DIFFERENT VIRAL INFECTIONS

Oncogenic impact of transformative viruses on the risk of cancer is well known. Today there are no studies focused on the effect of widespread, often persisting infections, such as herpes simplex virus (HSV), cytomegalovirus (CMV) and chlamydial infections on the level of hormones in the reproductive organs and their role in the pathogenesis of endometrial cancer. The aim of this study is to evaluate the effect of infectious agents in the substantive and concomitant conditions on the local hormone production in tissue of uterus and ovaries in patients with cancer of the body of uterus in menopausal age.In the tumor, in perifocal zone and in unaltered ovaries in patients with cancer of the body of uterus ELISA and PCR method determines the presence of herpes simplex virus types 1 and 2, cytomegalovirus and chlamydial infection. Depending on the level of infection in the tissues the local level of saturation of sex hormones, sex hormone binding globulin, prolactin were evaluated in samples of endometrium and ovaries. The presence of infectious agents have a modifying effect on local hormone production, increasing the intensity of disorders resulting in an imbalance of steroids, estrogen metabolites disturbance ratio and strengthening prolactinemia not only in tumor tissue but also in unchanged ovaries in patients with cancer of the body of uterus.

Effects of Rest Period/Number of Reps in Arm Specific Resistance Exercise on Acute Hormonal Responses

PURPOSE: In the present study, we investigated how resistance exercises with different rest times affect local hormone production. To determine the local hormonal responses induced by resistance exercise (RE), we designed RE protocols targeting the biceps and triceps muscles only. We hypothesize that short rest periods with light-medium weight/high reps induce higher hormonal responses than long rest periods with heavy weight/ lower reps. METHODS: 7 male students (24–37 yrs) were divided into 2 groups. All participants performed 3 exercises for biceps and triceps, respectively. For each exercise the participants executed 3 sets, each set taken to failure, the rest period between sets and exercises was 30 sec in the first groups (Short rest group, S). The weight was a weight the participants could perform between 15–25 reps (50% 1RM). The second group (Long rest group, L) performed the same training protocol except for the rest period between sets and exercises which has been lengthened to 3 min and the weight which has been increased to a max of 6–8 reps (80% 1RM). Blood collection was conducted immediately before, immediately after, 15 min, 30 min and 60 min after the exercise session. Blood samples were then analyzed for testosterone, free testosterone, IGF-1 and GH. The experiment was conducted twice with a recovery period of 2 months in a cross-over fashion in order to obtain n=8 for each group, each participant executing both RE protocols. RESULTS: The S group showed a significantly greater hormonal increase immediately after RE only in GH (282%, p<0.05 vs. rest, p<0.05 vs. before) . RE induced no significant changes in other anabolic hormones (testosterone, free testosterone and IGF-1). CONCLUSION: Arm only exercises can induce important acute hormonal increases if conducted with high intensity (short rest, high reps).

Are Hormones Relevant for the Search and Design of Anti-Parasitic Drugs?

Over the last years the biology of many parasites that infect humans and domestic animals has been intensively studied. Considerable efforts were addressed to obtain information on the parasite-host immune relationship. However, the knowledge of the endocrine physiology of parasites and the consequences of the local hormone production on the host tissues needs further investigation. We review here literature and our own studies on endocrine parasite capacities with special emphasis on cysticercosis. Besides the biological interest, these investigations may contribute to identify in the future alternative treatments for the disease.

Human granulosa-lutein cell in vitro production of progesterone, inhibin A, inhibin B, and activin A are dependent on follicular size and not the presence of the oocyte

To investigate inhibin A, inhibin B, activin A, and P production by cultured granulosa cells (GCs) and what relationship this hormone production has to fertility. Luteinized GCs from individual follicles were cultured, and inhibin A, inhibin B, activin A, and P production were measured by ELISA at 24 and 72 hours. Research laboratory and university hospital. Fifteen women who undertook an IVF-ICSI program, yielding 58 follicles. Individual follicular aspiration and preparation of GCs for culture. Inhibin A, inhibin B, activin A, and P production; oocyte retrieval; and fertility outcome. Inhibin A, inhibin B, and P continued to be secreted by GCs in vitro, and activin A levels were detected only marginally in 56% of cultures. The rate of production also was dependent on the size of follicle from which the GCs originated but not on oocyte presence or ability to fertilize. Granulosa cell stimulation with hCG had no effect on inhibin A but increased P and decreased inhibin B production. A marked effect of luteal differentiation appears to be the inhibition of inhibin B production in response to hCG stimulation. Luteinized GC function, with respect to inhibins, activin A, and P production, was not influenced by the presence or absence of an oocyte and did not correlate with fertility outcome. However, follicle size did influence rates of local hormone production.

Hormone cross-regulation in the tadpole brain: Developmental expression profiles and effect of T3 exposure on thyroid hormone- and estrogen-responsive genes in Rana pipiens

During metamorphosis, the tadpole neuroendocrine brain is a major target for the organisational effects of hormones acting via both endocrine feedback mechanisms and local hormone production. While the receptor-mediated actions of thyroid hormones in brain development have been well described, there is evidence that thyroid hormones could also be an important modulator of estrogen action during metamorphosis. To better understand hormone action and potential cross-regulation between thyroid hormone and estrogen, we examined changes in thyroid hormone receptors (TRα and TRβ) and the estrogen receptor (ERα) in the brain of Rana pipiens throughout metamorphosis and in response to 48 h waterborne triiodothyronine (T3) exposure (0.5, 5 and 50 nM). We also measured mRNA levels of iodothyronine deiodinase (D2 and D3) and aromatase, key enzymes responsible for local synthesis and availability of thyroid hormones and estrogen, respectively. A real-time PCR strategy targeting these genes was developed using either a fluorescent dual-labelled probe- or SYBR Green I-based method. TRβ mRNA levels were increased during development and in response to T3 exposure. Deiodinase (D2 and D3) enzymes were differentially regulated during development, but mRNA levels of both were increased with 50 nM T3 exposure. ERα and aromatase mRNA levels significantly increased at metamorphic climax, but whereas estrogen receptor alpha mRNA levels were increased by 50 nM T3, aromatase mRNA levels were decreased. These results (1) demonstrate that the developing amphibian brain is an important site for stage-specific thyroid hormone regulation of nuclear receptors and hormone synthesis enzymes and (2) provide the basis for further studies exploring the physiological and functional significance of the cross-regulation between thyroid status and estrogen-sensitive genes in the brain during amphibian metamorphosis.

Expression of leptin and its receptors in various tissues of ruminants

The energy metabolism of domestic animals is under the control of hormonal factors, which include thyroid hormones and leptin. Leptin signals from the periphery to the centre. It is mostly produced in the white adipose tissue and informs the central nervous system (CNS) about the total fat depot of the body. Low and high levels of leptin induce anabolic and catabolic processes, respectively. Besides controlling the food uptake and energy expenditure leptin is also involved in regulation of the reproduction and the immune system. Leptin is produced in several tissues other than fat. In the present paper the leptin expression of ruminant (Egyptian water buffalo, cow, and one-humped camel) tissues are examined. The mammary gland produces leptin in each species investigated. The local hormone production contributes to milk leptin and most probably helps to maintain lactation. Considerable leptin receptor expression was observed in the milk-producing epithelial cells, which is the same cell type that produces most of the udder leptin. Based on the results tissues participating in production have an autoregulative mechanism through which tissues can be relatively independent of the plasma leptin levels in order to maintain the desired function.

Effects of long and short hemodialysis on endothelial function: A short-term study

Endothelial dysfunction is common in end-stage renal disease and may contribute to the development of both hypertension and atherosclerosis. Long-slow hemodialysis (HD) has been associated with superior blood pressure control and fewer cardiovascular complications. We hypothesized that long dialysis times would improve endothelial function compared with shorter dialysis times. Eight long-term hemodialysis patients, not on antihypertensive drugs and with no evidence of vascular disease, were studied in a three-way randomized crossover-controlled trial. Each received, for one week and in randomized sequence, four hours of HD (SD), eight hours of HD, and eight hours of HD using a smaller dialyzer and slower blood pump. The same post-dialysis target weights were used with each treatment. On the third day of each treatment endothelium-dependent (flow mediated) and independent glyceryl trinitrate (GTN) induced vasodilation were measured by forearm strain-gauge plethysmography, and von Willebrand (vW) antigen, plasma homocysteine (tHcy) and neurohormones were measured pre- and post-dialysis. Despite achieving target post-dialysis weights with all treatments, pre-dialysis weight tended higher on SD. Endothelial dependent vasodilation increased after all HD treatments but did not differ between them. Adrenomedullin, N-terminal brain natriuretic peptide and vW antigen increased similarly across all HD whereas atrial and C-type natriuretic peptide, and endothelin-1 decreased across dialysis and were higher with SD. Pre-dialysis plasma tHcy concentrations were 13% higher during SD treatment. Hemodialysis improved endothelial-dependent vasodilation but the effect was similar with all three HD treatments. Improved endothelial function might result in part from altered local hormone production (endothelin-1 and adrenomedullin). These data suggest that increasing dialysis time is unlikely, in the short-term, to significantly improve endothelial function in patients with end-stage renal disease, but longer term studies are needed.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and PACAP-Receptor Type 1 Expression in Rat and Human Placenta1

Pituitary adenylate cyclase-activating polypeptide (PACAP), the new hypophysiotropic factor member of the vasoactive intestinal peptide (VIP)/secretin/glucagon/GHRH family of neuropeptides, exerts its biological action by interacting with both PACAP-selective type I receptors (PAC1) and type II receptors (VPAC1), which bind both PACAP and VIP. The placenta is a site of production of hypophysiotropic factors that participate in the control of local hormone production, as well as the respective hypothalamic-pituitary neurohormones. In the present study, we show the expression of PACAP gene and irPACAP distribution within rat and human placental tissues, by means of RT-PCR and immunohystochemical experiments. In both rat and human placenta, we evaluated the expression of PAC1 gene by Northern hybridization analysis performed with a 32P-labeled 706 nt complementary DNA probe, derived from the full-length coding region of the rPAC1 complementary DNA. The results of these experiments demonstrate the presence, in both human and rat placenta, of a 7.5-kb transcript similar in size to those detected in the ovary, brain, and hypothalamus. Alternative splicing of two exons occurs in human and rat PAC1 gene generating splice variants with variable tissue-specific expression. To ascertain which of the splice variants were expressed in placental tissue we performed RT-nested PCR using primers flanking the insertion sequence termed hip/hop cassette in rat or SV1/SV2 box in human gene. Electrophoretic analysis of the PCR products showed a different pattern of expression of messenger RNA splicing variants in human and rat placenta. In particular, the rat placenta expresses the short PAC1 receptor (PAC1short), the rPAC1-hip or hop (which are indistinguishable with the primers used), and the rPAC1-hip-hop, whereas the human placenta expresses only the PAC1SV1 (or SV2) variant, structurally homologous to the rat PAC1 hip (or hop). Sequence analysis of the human PCR-amplified PAC1 variant was therefore carried out and revealed that human placenta only expresses the PAC1SV2 isoform. The presence and characterization of PACAP binding sites was then investigated in human placenta by radioligand binding studies performed on crude membrane preparation using [125I]PACAP27 as tracer. Scatchard analysis of the binding results revealed the presence of two binding sites, one with high affinity and low capacity (Kd 0.33+/-0.04 nM; Bmax 36.9+/-12.1 fmol/mg protein) and one with low affinity and high capacity (Kd 24+/-6.9 nM, Bmax 9.3+/-0.19 pmol/mg protein). The relative potencies of PACAP-related peptides for inhibition ofradioligand binding were: PACAP27 > or = PACAP38 > VIP, whereas GHRH and other unrelated peptides, such as CRH and beta-endorphin, did not inhibit [125I]PACAP27 binding. In conclusion, in this study, we provide evidence for the expression of PACAP within rat and human placenta. We also demonstrate that both human and rat placenta express the PAC1 gene and that the human tissue has binding sites for PACAP. These findings may suggest a role for PACAP in the regulation of placental physiology through autocrine and/or paracrine mechanisms.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and PACAP-Receptor Type 1 Expression in Rat and Human Placenta

Pituitary adenylate cyclase-activating polypeptide (PACAP), the new hypophysiotropic factor member of the vasoactive intestinal peptide (VIP)/secretin/glucagon/GHRH family of neuropeptides, exerts its biological action by interacting with both PACAP-selective type I receptors (PAC1) and type II receptors (VPAC1), which bind both PACAP and VIP. The placenta is a site of production of hypophysiotropic factors that participate in the control of local hormone production, as well as the respective hypothalamic-pituitary neurohormones. In the present study, we show the expression of PACAP gene and irPACAP distribution within rat and human placental tissues, by means of RT-PCR and immunohystochemical experiments. In both rat and human placenta, we evaluated the expression of PAC1 gene by Northern hybridization analysis performed with a 32P-labeled 706 nt complementary DNA probe, derived from the full-length coding region of the rPAC1 complementary DNA. The results of these experiments demonstrate the presence, in both human and rat placenta, of a 7.5-kb transcript similar in size to those detected in the ovary, brain, and hypothalamus. Alternative splicing of two exons occurs in human and rat PAC1 gene generating splice variants with variable tissue-specific expression. To ascertain which of the splice variants were expressed in placental tissue we performed RT-nested PCR using primers flanking the insertion sequence termed hip/hop cassette in rat or SV1/SV2 box in human gene. Electrophoretic analysis of the PCR products showed a different pattern of expression of messenger RNA splicing variants in human and rat placenta. In particular, the rat placenta expresses the short PAC1 receptor (PAC1short), the rPAC1-hip or hop (which are indistinguishable with the primers used), and the rPAC1-hip-hop, whereas the human placenta expresses only the PAC1SV1 (or SV2) variant, structurally homologous to the rat PAC1 hip (or hop). Sequence analysis of the human PCR-amplified PAC1 variant was therefore carried out and revealed that human placenta only expresses the PAC1SV2 isoform. The presence and characterization of PACAP binding sites was then investigated in human placenta by radioligand binding studies performed on crude membrane preparation using [125I]PACAP27 as tracer. Scatchard analysis of the binding results revealed the presence of two binding sites, one with high affinity and low capacity (Kd 0.33 ± 0.04 nm; Bmax 36.9 ± 12.1 fmol/mg protein) and one with low affinity and high capacity (Kd 24 ± 6.9 nm, Bmax 9.3 ± 0.19 pmol/mg protein). The relative potencies of PACAP-related peptides for inhibition of radioligand binding were: PACAP27 ≥ PACAP38 > VIP, whereas GHRH and other unrelated peptides, such as CRH and β-endorphin, did not inhibit [125I]PACAP27 binding. In conclusion, in this study, we provide evidence for the expression of PACAP within rat and human placenta. We also demonstrate that both human and rat placenta express the PAC1 gene and that the human tissue has binding sites for PACAP. These findings may suggest a role for PACAP in the regulation of placental physiology through autocrine and/or paracrine mechanisms.

Transpleural gradient of 1,25-dihydroxyvitamin D in tuberculous pleuritis.

We used tuberculous pleuritis as a model to study the compartmentalization and potential immunoregulatory role of 1,25-dihydroxyvitamin D [1,25-(OH)2-D] in human granulomatous disease. In tuberculous pleuritis, mean concentrations of total 1,25-(OH)2-D were elevated in pleural fluid, compared to blood (67 pg/ml vs. 35 pg/ml). Concentrations of albumin, protein and 25-hydroxyvitamin D (25-OH-D) were lower in pleural fluid than blood, suggesting that accumulation of binding proteins does not explain the transpleural gradient of 1,25-(OH)2-D. The mean free 1,25-(OH)2-D concentration in pleural fluid was increased 5.3-fold over that in serum. 1,25-(OH)2-D3 inhibited PPD-induced proliferation of pleural fluid mononuclear cells, antigen-reactive lines and T lymphocyte clones derived from a single cell. Patient-derived PPD-reactive lines expressed a high-affinity intracellular binding moiety for 1,25-(OH)2-D3. Pleural fluid mononuclear cells and PPD-reactive lines did not metabolize 25-OH-D3 to 1,25-(OH)2-D3. The sum of these data suggests that concentration of 1,25-(OH)2-D in pleural fluid of tuberculosis patients is probably due to local hormone production by pleural tissue-based inflammatory cells that are not present in significant numbers in pleural fluid. Elevated concentrations of 1,25-(OH)2-D in pleural fluid may exert receptor-mediated inhibition of antigen-induced proliferation by pleural fluid lymphocytes. Inhibition of lymphocyte proliferation and lymphokine production may prevent tissue destruction from an uncontrolled inflammatory response.

The pattern of interstitial trophoblasticinvasion of the myometrium in early human pregnancy

The human placental bed myometrium, studied in 42 intact hysterectomy specimens ranging from 8 to 18 weeks' gestation, is characterized by the presence of large numbers of non-villous invasive cytotrophoblastic cells. Quantitative morphometric analysis reveals a tendency for maximal invasive activity to occur at the centre and, subsequently, to extend centrifugally to produce an annular pattern. Morphological observations suggest that the intimate mixture of cytotrophoblast with myometrial tissue must affect the mechanical properties of the myometrium. Local hormone production by trophoblast may induce or enhance these and other changes in uterine tissues that are essential for the establishment of human placentation. Cytotrophoblastic invasion into the myometrium appears to be restricted to the earlier stages of gestation and morphological evidence indicates that, subsequently, clumps of cytotrophoblast fuse to form multinuclear syncytiotrophoblast, the characteristic placental bed giant cells.

Prolactin production by placental membranes

The amniotic fluid contains high concentrations of prolactin. Using immunofluorescence and specific antibodies prolactin has been localized to the amnion and chorionic trophoblasts but not the placenta. The present study examines whether this staining reflects local hormone production by these tissues. Specimens of normal term decidua-chorion, amnion and placenta were organ cultured in medium M199 at 37°C for up to 120 h in 5% CO2 in oxygen and the prolactin levels of tissue homogenates and medium estimated by radioimmunoassay. Before culture higher prolactin concentrations were found in decidua-chorion and amnion than in placenta, while cultured decidua-chorion released significantly more prolactin into the culture medium than amnion or placenta. After 72 h culture, the prolactin concentrations of decidua-chorion remained high; the amnion approached placental levels. The protein inhibitors puromycin and cycloheximide substantially reduced the prolactin concentration in both cultured decidua-chorion and its incubation medium. Throughout the experiments the cultured tissue remained viable and showed only minimal degeneration. It is concluded that human decidua-chorion synthesizes prolactin and this tissue is a major source of amniotic fluid prolactin. Chorionic trophoblasts are postulated as a cellular source of prolactin while amnion binds this hormone. Abnormalities of chorionic prolactin synthesis may be important in the pathogenesis of oligo- or polyhydramnios and prematurity. The amniotic fluid contains high concentrations of prolactin. Using immunofluorescence and specific antibodies prolactin has been localized to the amnion and chorionic trophoblasts but not the placenta. The present study examines whether this staining reflects local hormone production by these tissues. Specimens of normal term decidua-chorion, amnion and placenta were organ cultured in medium M199 at 37°C for up to 120 h in 5% CO2 in oxygen and the prolactin levels of tissue homogenates and medium estimated by radioimmunoassay. Before culture higher prolactin concentrations were found in decidua-chorion and amnion than in placenta, while cultured decidua-chorion released significantly more prolactin into the culture medium than amnion or placenta. After 72 h culture, the prolactin concentrations of decidua-chorion remained high; the amnion approached placental levels. The protein inhibitors puromycin and cycloheximide substantially reduced the prolactin concentration in both cultured decidua-chorion and its incubation medium. Throughout the experiments the cultured tissue remained viable and showed only minimal degeneration. It is concluded that human decidua-chorion synthesizes prolactin and this tissue is a major source of amniotic fluid prolactin. Chorionic trophoblasts are postulated as a cellular source of prolactin while amnion binds this hormone. Abnormalities of chorionic prolactin synthesis may be important in the pathogenesis of oligo- or polyhydramnios and prematurity.