scholarly journals Reduced Hypothalamic Vasopressin Secretion Underlies Attenuated Adrenocorticotropin Stress Responses in Pregnant Rats

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1626-1637 ◽  
Author(s):  
Shuaike Ma ◽  
Michael J. Shipston ◽  
David Morilak ◽  
John A. Russell
Keyword(s):  
Mrna Expression ◽  
Anterior Pituitary ◽  
Late Pregnancy ◽  
Secretory Response ◽  
Receptor Expression ◽  
Pituitary Cells ◽  
Pregnant Rats ◽  
V1b Receptor ◽  
Vasopressin Secretion ◽  
In Pregnancy

We sought to explain decreased ACTH secretory responses to stress in pregnant rats by investigating hypothalamic CRH and vasopressin secretion and actions on anterior pituitary corticotrophs. In late pregnancy median eminence, CRH content was reduced (by 12%). Anterior pituitary proopiomelanocortin mRNA expression, measured by in situ hybridization but not radioimmunoassayed ACTH content, was also reduced (by 45% on d 21); CRH receptor (CRHR)1 mRNA expression was unaltered in pregnancy, but V1b receptor mRNA expression was reduced (by 19%). ACTH secretory responses, measured in jugular blood, to CRH (200 ng/kg iv) or vasopressin (1.7 μg/kg, iv) were reduced on d 21 vs. virgins (49% and 44%), but the response to combined CRH and vasopressin injection was intact. Either antalarmin (CRHR1 antagonist; 20 mg/kg ip) or dP(Tyr(Me)2),Arg-NH29)AVP (V1a/b antagonist; 10 μg/kg, iv) pretreatment reduced the ACTH secretory response to forced swimming (90 sec) in virgin rats (by 57% and 40%), but only antalarmin was effective in pregnant rats (53% decrease). In vitro, measuring ACTH secretion from acutely dispersed anterior pituitary cells showed increased corticotroph sensitivity in pregnancy to CRH and to CRH augmentation by vasopressin, attributable to increased intracellular cAMP action. Hence, in late pregnancy, reduced anterior pituitary CRHR1 or V1b receptor expression did not impair corticotroph responses to CRH or vasopressin. Rather, diminished secretagogue secretion in vivo accounts for reduced action of stress levels of exogenous CRH or vasopressin alone; the late pregnancy attenuated ACTH secretory response to swim stress is deduced to be due to reduced vasopressin release by parvocellular paraventricular nuclei neurones.

scholarly journals Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention

2015 ◽  
Vol 309 (1) ◽  
pp. F63-F70 ◽  
Author(s):  
Crystal A. West ◽  
Alicia A. McDonough ◽  
Shyama M. E. Masilamani ◽  
Jill W. Verlander ◽  
Chris Baylis
Keyword(s):  
Mrna Expression ◽  
Regional Differences ◽  
Late Pregnancy ◽  
Kidney Cortex ◽  
Apical Region ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Apical Localization ◽  
In Pregnancy

Pregnancy is characterized by plasma volume expansion due to Na+ retention, driven by aldosterone. The aldosterone-responsive epithelial Na+ channel is activated in the kidney in pregnancy. In the present study, we investigated the aldosterone-responsive Na+-Cl− cotransporter (NCC) in mid- and late pregnant rats compared with virgin rats. We determined the abundance of total NCC, phosphorylated NCC (pNCC; pT53, pS71 and pS89), phosphorylated STE20/SPS-1-related proline-alanine-rich protein kinase (pSPAK; pS373), and phosphorylated oxidative stress-related kinase (pOSR1; pS325) in the kidney cortex. We also measured mRNA expression of NCC and members of the SPAK/NCC regulatory kinase network, serum and glucocorticoid-regulated kinase (SGK)1, total with no lysine kinase (WNK)1, WNK3, and WNK4. Additionally, we performed immunohistochemistry for NCC kidneys from virgin and pregnant rats. Total NCC, pNCC, and pSPAK/OSR1 abundance were unchanged in midpregnant versus virgin rats. In late pregnant versus virgin rats, total NCC and pNCC were decreased; however, pSPAK/OSR1 was unchanged. We detected no differences in mRNA expression of NCC, SGK1, total WNK1, WNK3, and WNK4. By immunohistochemistry, NCC was mainly localized to the apical region in virgin rats, and density in the apical region was reduced in late pregnancy. Therefore, despite high circulating aldosterone levels in pregnancy, the aldosterone-responsive transporter NCC is not increased in total or activated (phosphorylated) abundance or in apical localization in midpregnant rats, and all are reduced in late pregnancy. This contrasts to the mineralocorticoid-mediated activation of the epithelial Na+ channel, which we have previously reported. Why and how NCC escapes aldosterone activation in pregnancy is not clear but may relate to regional differences in aldosterone sensitivity the increased K+ intake or other undefined mechanisms.

scholarly journals Estrogen receptor α-induced cholecystokinin type A receptor expression in the female mouse pituitary

2007 ◽  
Vol 195 (3) ◽  
pp. 393-405 ◽  
Author(s):  
Hyun Joon Kim ◽  
Mary C Gieske ◽  
Susan Hudgins ◽  
Beob Gyun Kim ◽  
Andree Krust ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Mrna Expression ◽  
Anterior Pituitary ◽  
Critical Role ◽  
Type A ◽  
Estrogen Receptor Α ◽  
Receptor Expression ◽  
Pituitary Cells ◽  
Mouse Pituitary ◽  
Lh Secretion

Estrogen plays a critical role in inducing LH surge. In the pituitary, estrogen receptor α (ERα) mediates the action of estrogen, while the downstream pathway of ERα activation is yet to be elucidated. Here, we report the finding that cholecystokinin type A receptor (CCK-AR) is an ERα downstream gene in the mouse anterior pituitary. In the cycling mouse pituitary, the expression of CCK-AR mRNA is markedly higher in the afternoon of proestrus compared with metestrus. Both ovariectomy (OVX) and null mutation of the ERα gene completely abolish CCK-AR mRNA expression. Injection of 17β-estradiol to OVX wild-type mice induces recovery of CCK-AR mRNA expression to levels observed at proestrus, but no such recovery is induced in OVX ERα knockout mice. The same pattern of estrogen dependency in inducing CCK-AR mRNA expression was seen in cultured primary anterior pituitary cells, indicating that estrogen directly acts on pituitary cells to induce CCK-AR expression. Immunohistological analysis revealed that more than 80% of gonadotrophs express CCK-AR in the afternoon of proestrus. To test whether CCK-AR mediated the sensitizing effect of estrogen in GnRH-induced LH secretion, primary pituitary cells were primed with estrogen followed by treatment with GnRH in the presence or absence of lorglumide, a CCK-AR antagonist. While both groups secreted LH upon GnRH treatment, lorglumide treatment significantly decreased LH secretion. Taken together, this study finds CCK-AR to be an ERα downstream gene in the pituitary and suggests that CCK-AR may play a role in the estrogen sensitization of the pituitary response to GnRH.

scholarly journals Leptin and Leptin Receptor Expression in Normal and Neoplastic Human Pituitary: Evidence of a Regulatory Role for Leptin on Pituitary Cell Proliferation1

1999 ◽  
Vol 84 (8) ◽  
pp. 2903-2911 ◽  
Author(s):  
Long Jin ◽  
Bartolome G. Burguera ◽  
Marta E. Couce ◽  
Bernd W. Scheithauer ◽  
Jesse Lamsan ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
Leptin Receptor ◽  
Pituitary Cell ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Pituitary Cells ◽  
Double Labeling ◽  
Messenger Ribonucleic Acid ◽  
Anterior Pituitary Cell ◽  
Anterior Pituitary Cells

Leptin is a circulating hormone secreted by adipose and a few other tissues. The leptin receptor consists of a single transmembrane-spanning polypeptide that is present as a long physiologically important form as well as in several short isoforms. Recent studies have suggested that the anterior pituitary may have a role in the regulatory effects of leptin in animal models. To test this possibility in human pituitaries, we examined the expression of leptin and OB-R in normal and neoplastic pituitaries, and the possible functions of leptin in the pituitary were also analyzed. Leptin was present in 20–25% of anterior pituitary cells and was expressed in most normal anterior pituitary cells, including ACTH (70% of ACTH cells), GH (21%), FSH (33%), LH (29%), TSH (32%), and folliculo-stellate cells (64%), but was colocalized with very few PRL cells (3%), as detected by double labeling immunohistochemistry with two different antileptin antibodies. In addition, leptin expression was detected by RT-PCR in some pituitary tumors, including ACTH (three of four), GH (one of four), null cells (two of four), and gonadotroph (one of four) tumors as well as in normal pituitary. Immunohistochemical staining showed greater immunoreactivity for leptin in normal pituitaries compared to adenomas. Treatment of an immortalized cultured anterior pituitary cell line, HP75, with leptin stimulated pancreastatin secretion in vitro. Leptin also inhibited cell growth in the human HP75 and in the rat pituitary GH3 cell lines. Both long (OB-Rb) and common (OB-Ra) forms of the leptin receptor messenger ribonucleic acid and leptin receptor protein were expressed in normal and neoplastic anterior pituitary cells. These findings show for the first time that leptin is expressed by most human anterior pituitary cell types and that there is decreased leptin protein immunoreactivity in pituitary adenomas compared to that in normal pituitary tissues. We also show that OB-Rb is widely expressed by normal and neoplastic anterior pituitary cells, implicating an autocrine/paracrine loop in the production and regulation of leptin in the pituitary.

Secretion of adrenocorticotrophin (ACTH) and ACTH precursors in ovine anterior pituitary cells: actions of corticotrophin-releasing hormone, arginine vasopressin and glucocorticoids

1994 ◽  
Vol 140 (2) ◽  
pp. 189-195 ◽  
Author(s):  
J Schwartz ◽  
P Ash ◽  
V Ford ◽  
H Raff ◽  
S Crosby ◽  
...  
Keyword(s):  
Arginine Vasopressin ◽  
Anterior Pituitary ◽  
Secretory Response ◽  
Target Cells ◽  
Pituitary Cells ◽  
Basal Secretion ◽  
Acth Secretion ◽  
Releasing Hormone ◽  
Anterior Pituitary Cells ◽  
Synthetic Glucocorticoid

Abstract Although corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) have been extensively characterized as stimulators, and glucocorticoids as inhibitors of ACTH secretion, far less is known about the control of the secretion of ACTH precursors from the anterior pituitary or about the types of corticotrophs involved. The present study was designed to systematically evaluate the actions of stimulatory and inhibitory factors on the secretion of ACTH and ACTH precursors (pro-opiomelanocortin, Mr 31 000; pro-ACTH, Mr 22 000) from dissociated ovine anterior pituitary cells. The cells were stimulated for 3 h with CRH (10 nmol/l) and AVP (100 nmol/l), alone or in combination with the synthetic glucocorticoid dexamethasone. In designated wells, cells were treated with dexamethasone, (100 nmol/l), beginning 16–18 h before and continuing through the 3-h secretion experiments in the presence of CRH and AVP. Secretion of ACTH-like peptides from intact cultures was compared with that from cultures which had been pretreated with a cytotoxic CRH conjugate (cytotoxin) to eliminate CRH-target cells specifically. Immunoreactive (ir)-ACTH was measured by radioimmunoassay (RIA); ACTH(1–39) and ACTH precursors were specifically measured by two-site immunoradiometric assays that discriminate between the two. In intact populations of cells, dexamethasone had no effect on basal ACTH(1–39) secretion, but decreased the secretion of ACTH(1–39) in response to CRH or AVP. Pretreatment of cells in the same experiments with cytotoxin (for 18 h, beginning 3·5 days before secretion studies) also had no significant effect on basal ACTH(1–39) secretion, but eliminated the response to CRH and decreased the response to AVP. In contrast to the situation in intact populations, dexamethasone had no effect on the residual secretion of ACTH(1–39) in response to AVP. These results mirrored those for secretion of ir-ACTH, measured by RIA. Secretion of ACTH precursors followed a different pattern from that for ir-ACTH and ACTH(1–39). In intact populations, dexamethasone decreased the secretion of ACTH precursors in response to CRH, but had no effect on basal secretion or the precursor response to AVP. Elimination of CRH-target cells also had no effect on basal precursor secretion and eliminated the secretion of precursors in response to CRH. Loss of CRH-target cells was accompanied by a smaller decrease in the secretion of ACTH precursors than ir-ACTH and ACTH(1–39) in response to AVP. Interestingly, dexamethasone significantly increased the secretion of ACTH precursors in response to AVP after cytotoxin. These results suggest either that the inhibition by glucocorticoids of the ACTH(1–39) secretory response to AVP is confined to those AVP-responsive cells that are sensitive to the CRH-target-specific cytotoxin, or that glucocorticoid-induced inhibition of the response to AVP depends on the functional presence of CRH-responsive cells. The results further suggest that the secretion of ACTH precursors in response to AVP is resistant to inhibition by glucocorticoids, regardless of the presence of CRH-target cells and is, generally, much less influenced by, or dependent upon, CRH-target cells. Taken together, the data suggest that those corticotrophs which are resistant to cytotoxin are the source of ACTH precursors secreted in response to AVP, and resist inhibition by glucocorticoids. Journal of Endocrinology (1994) 140, 189–195

scholarly journals Streptozotocin-Induced Diabetes Decreases Mammary Gland Lipoprotein Lipase Activity and Messenger Ribonucleic Acid in Pregnant and Nonpregnant Rats

2002 ◽  
Vol 3 (1) ◽  
pp. 61-68
Author(s):  
Laura Blanco-Dolado ◽  
Antonia Martín-Hidalgo ◽  
Emilio Herrera
Keyword(s):  
Mammary Gland ◽  
Mrna Expression ◽  
Lipoprotein Lipase ◽  
Late Pregnancy ◽  
Insulin Deficiency ◽  
Pregnant Rats ◽  
Messenger Ribonucleic Acid ◽  
Mrna Content ◽  
Plasma Insulin Levels ◽  
Streptozotocin Induced Diabetes

Diabetes mellitus is associated with a reduction of lipoprotein lipase (LPL) activity in adipose tissue and development of hypertriglyceridemia. To determine how a condition of severe insulin deficiency affects mammary gland LPL activity and mRNA expression during late pregnancy, streptozotocin (STZ) treated (40 mg/kg) and non-treated (control) virgin and 20 day pregnant rats were studied. In control rats, both LPL activity and mRNA were higher in pregnant than in virgin rats. When compared to control rats, STZ-treated rats, either pregnant or virgin, showed decreased LPL activity and mRNA content. Furthermore, mammary gland LPL activity was linearly correlated with mRNA content, and either variable was linearly correlated with plasma insulin levels. Thus, insulin deficiency impairs the expression of LPL in mammary glands, revealing the role of insulin as a modulator of the enzyme at the mRNA expression level.

scholarly journals Maximal expression of suppressors of cytokine signaling in the rat ovary occurs in late pregnancy

Reproduction ◽  
2009 ◽  
Vol 138 (3) ◽  
pp. 537-544 ◽  
Author(s):  
Stephen T Anderson ◽  
Naajia N M Isa ◽  
Johanna L Barclay ◽  
Michael J Waters ◽  
Jon D Curlewis
Keyword(s):  
Mrna Expression ◽  
Prolactin Receptor ◽  
Prostaglandin F2α ◽  
Late Pregnancy ◽  
Placental Lactogen ◽  
Cytokine Signaling ◽  
Pregnant Rats ◽  
Protein Levels ◽  
Rat Ovary ◽  
Suppressors Of Cytokine Signaling

Maintenance of the rodent corpus luteum (CL) during pregnancy requires prolactin receptor (PRLR) signal transduction via STAT5. At the end of pregnancy, prostaglandin F2α (PGF2α) induces luteal regression through many mechanisms, including downregulation of PRLR signaling. We have previously shown that a PGF2α analog upregulates suppressors of cytokine signaling (SOCS) proteins in the CL of day 19 pregnant rats leading to reduced STAT5 signaling. Here, we examined endogenous SOCS expression and STAT5 signaling in the rat ovary during normal pregnancy and luteolysis. The mRNA expression of Socs1, Socs2, and Socs3 and related cytokine-inducible SH2-containing protein (Cish) was low in early pregnancy (day 7), but significantly increased at mid-pregnancy (days 10 and 13) associated with increased endogenous tyrosine phosphorylation (TyrP) of STAT5. In support of the notion that these changes are due to increasing placental lactogen levels at this time, we found that treatment with exogenous PRL on day 7 increased TyrP of STAT5 and induced SOCS mRNA expression, except Socs3. After mid-pregnancy, further significant increases in Socs3 and Cish mRNA expression were observed. Such changes in mRNA expression correlated with protein levels, with protein levels of both SOCS3 and CISH being maximal in late pregnancy (days 19–21). In addition, a significant reduction in TyrP of STAT5 was first observed on day 20, with a further substantial decrease on day 21. Therefore, these results are consistent with the hypothesis that increased SOCS expression in the rat ovary during late pregnancy reduces STAT5 signaling, which may be important in PGF2α-induced luteolysis.

INSULIN SECRETORY RESPONSE OF ISOLATED ISLETS OF LANGERHANS IN PREGNANT RATS: EFFECTS OF DIETARY RESTRICTION

1974 ◽  
Vol 62 (1) ◽  
pp. 137-143 ◽  
Author(s):  
I. C. GREEN ◽  
K. W. TAYLOR
Keyword(s):  
Insulin Secretion ◽  
Food Intake ◽  
Islets Of Langerhans ◽  
Secretory Response ◽  
Pregnant Rats ◽  
Additional Food ◽  
Daily Food ◽  
Isolated Islets Of Langerhans ◽  
Low Glucose ◽  
In Pregnancy

SUMMARY The effects of diet on the altered insulin secretory responses of islets of Langerhans of pregnant rats have been investigated. The daily food intake of pregnant rats was found to exceed that of control non-pregnant rats by 20% on average. Depriving pregnant rats of this additional food resulted in an alteration in the pattern of insulin secretion seen in pregnancy, such that the sensitivity to stimulation by low glucose concentrations was abolished. The contribution made by different components of the diet to the secretory response in pregnancy was investigated. When additional carbohydrate, though not protein, was fed to pregnant rats on a restricted food intake, the sensitivity of the islets to glucose stimulation was restored. It was concluded that the quantity and in particular the carbohydrate content of food eaten by pregnant rats exerts an important influence on the changes in insulin secretion in pregnancy.

scholarly journals Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

2015 ◽  
Vol 309 (12) ◽  
pp. R1553-R1568 ◽  
Author(s):  
K. Max Coldren ◽  
Randall Brown ◽  
Eileen M. Hasser ◽  
Cheryl M. Heesch
Keyword(s):  
Blood Volume ◽  
Paraventricular Nucleus ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Receptor Expression ◽  
Ang Ii ◽  
Transient Effects ◽  
Nerve Activity ◽  
Pregnant Rats ◽  
In Pregnancy

Pregnancy is characterized by increased blood volume and baseline sympathetic nerve activity (SNA), vasodilation, and tachycardia. Relaxin (RLX), an ovarian hormone elevated in pregnancy, activates forebrain sites involved in control of blood volume and SNA through ANG II-dependent mechanisms and contributes to adaptations during pregnancy. In anesthetized, arterial baroreceptor-denervated nonpregnant (NP) rats, RLX microinjected into the subfornical organ (SFO; 0.77 pmol in 50 nl) produced sustained increases in lumbar SNA (8 ± 3%) and mean arterial pressure (MAP; 26 ± 4 mmHg). Low-dose intracarotid artery infusion of RLX (155 pmol·ml−1·h−1; 1.5 h) had minor transient effects on AP and activated neurons [increased Fos-immunoreactivity (IR)] in the SFO and in spinally projecting (19 ± 2%) and arginine-vasopressin (AVP)-IR (21 ± 5%) cells in the paraventricular nucleus of the hypothalamus of NP, but not pregnant (P), rats. However, mRNA for RLX and ANG II type 1a receptors in the SFO was preserved in pregnancy. RLX receptor-IR is present in the region of the SFO in NP and P rats and is localized in astrocytes, the major source of angiotensinogen in the SFO. These data provide an anatomical substrate for a role of RLX in the resetting of AVP secretion and increased baseline SNA in pregnancy. Since RLX and ANG II receptor expression was preserved in the SFO of P rats, we speculate that the lack of response to exogenous RLX may be due to maximal activation by elevated endogenous levels of RLX in near-term pregnancy.

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