POSSIBLE ROLE OF 5α-ANDROSTANE-3α,17β-DIOL IN THE CONTROL OF FOLLICLE-STIMULATING HORMONE SECRETION IN THE IMMATURE FEMALE RAT

1982 ◽  
Vol 92 (1) ◽  
pp. 37-42 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS ◽  
P. KRAMER ◽  
L. GRIBLING-HEGGE

A possible role of 5α-androstane-3α,17β-diol (3α-androstanediol) in the control of FSH secretion was studied at various ages in ovariectomized rats. In the rat strain used, vaginal opening, coincident with first ovulation, generally occurs between 37 and 42 days of age. If 3α-androstanediol alone was given as an ovarian substitute, an inhibitory effect on FSH release was evident with all three doses tested (50, 100, 300 μg/100 g body wt) between 13 and 30 days of age; at 33–35 days of age only the 300 μg dose caused some inhibition of FSH release. Results were more complex if 3α-androstanediol was given in combined treatment with oestradiol and progesterone. Given with progesterone, 3α-androstanediol showed a synergistic inhibitory action on FSH release between 20 and 30 days of age. However, when 3α-androstanediol was combined with oestradiol a clear decrease in effect, as compared to the effect of oestradiol alone, was found between 20 and 30 days of age. Also the effect of combined oestradiol and progesterone treatment was greater than the effect of combined treatment with oestradiol, progesterone and 3α-androstanediol. At all ages after day 20 none of the steroid combinations tested was capable of maintaining FSH levels in ovariectomized rats similar to those in intact rats. It is concluded that 3α-androstanediol might play a role in the control of FSH secretion in the immature rat, but after day 20 the potentially inhibitory action of 3α-androstanediol on FSH secretion is limited in the presence of oestradiol.

1981 ◽  
Vol 89 (1) ◽  
pp. 99-106 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS ◽  
P. KRAMER ◽  
L. GRIBLING-HEGGE

The inhibitory action on FSH secretion of combined oestradiol and progesterone treatment of ovariectomized, immature rats was studied at various ages. At all ages studied (13–35 days) an additional inhibitory action of progesterone, if combined with oestradiol, could be found as compared with the effect of oestradiol alone. Until 20 days of age, the rise in serum FSH concentration as measured 2 days after ovariectomy could be completely prevented by administration of 0·05 μg oestradiol/100 g body weight or by administration of a lower dose of oestradiol (0·01–0·025 μg) combined with progesterone (0·5–1·5 mg/100 g body weight). After 20 days neither oestradiol nor the combined oestradiol/progesterone treatment resulted in an FSH concentration similar to that found in intact rats. However, the lowest FSH concentrations were reached by using combinations of oestradiol and progesterone. Using progesterone alone, FSH concentration in ovariectomized rats was significantly reduced between 18 and 30 days of age, but not before or after this period. Taken together with data on uterine weight and serum concentrations of progesterone, these findings suggest that (1) both oestradiol and progesterone exert an age-dependent role in regulating FSH secretion in the immature female rat, and (2) amounts of oestradiol and progesterone capable of maintaining, in ovariectomized rats, uterine weights not different from those in intact rats will maintain near-physiological concentrations of FSH before but not after day 20. Thus, ovarian factors other than oestradiol and progesterone must be involved in the regulation of FSH secretion in the female rat after 20 days of age.


1979 ◽  
Vol 81 (2) ◽  
pp. 199-208 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS ◽  
P. KRAMER

The maturation of the inhibitory feedback action of oestrogen on FSH secretion in the immature female rat was studied from 5 days of age until after the first ovulation. To study the role of the oestrogen binding alpha-foetoprotein (AFP) which is present in the blood of young animals, the effects of various doses of oestradiol and of the synthetic oestrogen R2858 (11β-methoxy-17-ethynyl-oestradiol), which is not bound by AFP, were compared in ovariectomized rats. A rise in the serum concentration of FSH within 2 days of ovariectomy was first observed in rats ovariectomized at 8 days of age. Between 8 and 28 days of age the rise in FSH after ovariectomy could be prevented by oestrogen injections in such a way that the resulting FSH concentration amounted to 50% of that in ovariectomized control rats. This was achieved with a constant dose of 0·00015 μg R2858/100 g body weight, whereas the dose of oestradiol needed decreased from 0·05 to 0·01 μg/100 g body weight indicating an increased sensitivity to the feedback action of oestradiol. After day 28, sensitivity to the feedback action of both R2858 and oestradiol decreased progressively up to the time of the first ovulation. In contrast to results at earlier ages, none of the doses of either oestrogen was capable of maintaining near-physiological concentrations of FSH after 20 days of age. It is concluded that the apparent increase in sensitivity to the feedback action of oestradiol occurring before 28 days of age reflects the disappearance of AFP from the blood, whereas the subsequent decrease in sensitivity is independent of AFP. Moreover, it is concluded that up to about 20 days of age oestradiol could be, though not necessarily is, the sole ovarian factor involved in regulating FSH secretion, whereas at later ages additional steroids and/or factors must be involved.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3071 ◽  
Author(s):  
Giustino Orlando ◽  
Sheila Leone ◽  
Claudio Ferrante ◽  
Annalisa Chiavaroli ◽  
Adriano Mollica ◽  
...  

Besides its role as key regulator in gonadotropin releasing hormone secretion, reproductive function, and puberty onset, kisspeptin has been proposed to act as a bridge between energy homeostasis and reproduction. In the present study, to characterize the role of hypothalamic kisspeptin as metabolic regulator, we evaluated the effects of kisspeptin-10 on neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF) gene expression and the extracellular dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytriptamine, 5-HT), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIIA) concentrations in rat hypothalamic (Hypo-E22) cells. Our study showed that kisspeptin-10 in the concentration range 1 nM–10 μM was well tolerated by the Hypo-E22 cell line. Moreover, kisspeptin-10 (100 nM–10 μM) concentration independently increased the gene expression of NPY while BDNF was inhibited only at the concentration of 10 μM. Finally, kisspeptin-10 decreased 5-HT and DA, leaving unaffected NE levels. The inhibitory effect on DA and 5-HT is consistent with the increased peptide-induced DOPAC/DA and 5-HIIA/5-HT ratios. In conclusion, our current findings suggesting the increased NPY together with decreased BDNF and 5-HT activity following kisspeptin-10 would be consistent with a possible orexigenic effect induced by the peptide.


2004 ◽  
Vol 286 (5) ◽  
pp. R888-R893 ◽  
Author(s):  
Sook Jeong Lee ◽  
Carol S. Landon ◽  
Stanley J. Nazian ◽  
John R. Dietz

We examined the role of cytochrome P-450-arachidonate (CYP450-AA) metabolites in endothelin-1 (ET-1)-stimulated atrial natriuretic peptide (ANP) and pro-ANP-(1-30) secretion from the heart. 17-Octadecynoic acid (17-ODYA, 10-5 M) significantly inhibited ANP secretion stimulated by ET-1 (10-8 M) in the isolated perfused rat atria and inhibited pro-ANP-(1-30) secretion stimulated by ET-1 (10-8 M) or 20-hydroxyeicosatetraenoic acid in cultured neonatal rat ventricular myocytes (NRVM). In NRVM, 17-ODYA significantly ( P < 0.05) increased secretion of cAMP but had no significant effect on the secretion of cGMP from NRVM. Staurosporine, an inhibitor of protein kinase C, completely blocked the inhibitory action of 17-ODYA, whereas a protein kinase A inhibitor, H-89 (5 × 10-5 M), did not significantly attenuate the effects of 17-ODYA. The results show that the inhibitory action of 17-ODYA on ET-1-augmented ANP secretion is mediated through cAMP and suggest that CYP450-AA may play an important role in ET-1-induced cardiac hormone secretion.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Victor M Pulgar ◽  
Liliya M Yamaleyeva ◽  
Jasmina Varagic ◽  
Carolynne M McGee ◽  
Michael Bader ◽  
...  

The balance between vasodilatory and vasoconstrictor prostanoids contributes to vascular control during pregnancy. Alterations in this balance are involved in the development of hypertensive pregnancy. The transgenic female rat containing the human angiotensinogen (hAGN) gene mated with the male transgenic containing human renin (hREN) is a model of preeclampsia (TgA), and shows hypertension and proteinuria at late gestation. We investigated the role COX-derived mediators have on contractility of the uterine artery (UA) in TgA rats before the hypertensive phenotype develops. UA were isolated from transgenic TgA (n=9) and Sprague-Dawley (n=7) control rats at 7 days of gestation. UA were mounted in a wire myograph for determinations of isometric tension (DMT USA, 620M). Responses to acetylcholine (ACh), phenylephrine (Phe) and sodium nitroprusside (SNP) were measured in control conditions and after preincubation with indomethacin (Indo, 10-5M). Data were fitted to a dose response curve, vasodilatation was expressed as percent of pre-constriction and sensitivity as pD2 (pD2= -Log [EC50]). Responses to ACh reached similar maximal relaxations (64±8 vs 75±6%, p>0.05), and an increased contraction in TgA UA at ACh >10μM (p<0.05) was eliminated by Indo. Contraction to Phe was similar in both groups with an inhibitory effect of Indo on TgA UA (p<0.05). Relaxation to SNP was lower in TgA vs SD UA (92±2 vs 74±5%, p<0.05), this difference was abolished by Indo. Thus, inhibition of COX enzymes had a greater effect on TgA UA suggesting an imbalance towards an increased prostanoids-derived constrictor tone in TgA UA. This imbalance appears before the hypertensive phenotype is established.


2005 ◽  
Vol 94 (1) ◽  
pp. 612-621 ◽  
Author(s):  
Robert A. Rose ◽  
Madhu B. Anand-Srivastava ◽  
Wayne R. Giles ◽  
Jaideep S. Bains

Magnocellular neurosecretory cells (MNCs), of the paraventricular and supraoptic nuclei of the hypothalamus, secrete the hormones vasopressin and oxytocin. As a result, they have an essential role in fundamental physiological responses including regulation of blood volume and fluid homeostasis. C-type natriuretic peptide (CNP) is present at high levels in the hypothalamus. Although CNP is known to decrease hormone secretion from MNCs, no studies have examined the role of the natriuretic peptide C receptor (NPR-C) in these neurons. In this study, whole cell recordings from acutely isolated MNCs, and MNCs in a coronal slice preparation, show that CNP (2 × 10−8 M) and the selective NPR-C agonist, cANF (2 × 10−8 M), significantly inhibit L-type Ca2+ current ( ICa(L)) by ∼50%. This effect on ICa(L) is mimicked by dialyzing a Gi-activator peptide (10−7 M) into these cells, implicating a role for the inhibitory G protein, Gi. These NPR-C–mediated effects were specific to ICa(L). T-type Ca2+ channels were unaffected by CNP. Current-clamp experiments revealed the ability of CNP, acting via the NPR-C receptor, to decrease (∼25%) the number of action potentials elicited during a 500 ms depolarizing stimulus. Analysis of action potential duration revealed that CNP and cANF significantly decreased 50% repolarization time (APD50) in MNCs. In summary, our findings show that CNP has a potent and selective inhibitory effect on ICa(L) and on excitability in MNCs that is mediated by the NPR-C receptor. These data represent the first electrophysiological evidence of a functional role for the NPR-C receptor in the mammalian hypothalamus.


2010 ◽  
Vol 23 (1) ◽  
pp. 3-11 ◽  
Author(s):  
X. F. Li ◽  
Y. S. Lin ◽  
J. S. Kinsey-Jones ◽  
S. R. Milligan ◽  
S. L. Lightman ◽  
...  

2002 ◽  
Vol 282 (1) ◽  
pp. F144-F150 ◽  
Author(s):  
Bruno A. Escalante ◽  
John C. McGiff ◽  
Adebayo O. Oyekan

We examined the rat proximal tubule (PT) response to endothelin-1 (ET-1) in terms of 20-hydroxyeicosatetraenoic acid (HETE) dependency. Arachidonic acid (AA) (1 μM) decreased ouabain-sensitive 86Rb uptake from 2.1 ± 0.1 to 0.3 ± 0.08 ng Rb · 10 μg protein−1 · 2 min−1( P < 0.05); 20-HETE (1 μM) had similar effects. Dibromododecenoic acid (DBDD) (2 μM), an inhibitor of ω-hydroxylase, abolished the inhibitory action of AA on86Rb uptake whereas the PT response to 20-HETE was unaffected. ET-1 at 0.1, 1, 10, and 100 nM reduced 86Rb uptake from 2.8 ± 0.3 in control PTs to 2.4 ± 0.2, 1.7 ± 0.1, 0.67 ± 0.08, and 0.1 ± 0.03 ng Rb · 10 μg protein−1 · 2 min−1, respectively. DBDD (2 μM) abolished the inhibitory effect of ET-1 on86Rb uptake as did BMS182874 (1 μM), an ETA-selective receptor antagonist. ET-1 (100 nM) significantly increased PT 20-HETE release by ∼50%, an effect prevented by DBDD. N ω-nitro-l-arginine-methyl ester (l-NAME), given for 4 days to inhibit nitric oxide synthase (NOS), increased arterial pressure from 92 ± 12 to 140 ± 8 mmHg and increased endogenous release of 20-HETE from isolated PTs (measured by gas chromatography/mass spectrometry). Inl-NAME-treated PTs, but not in control PTs, 0.1 μM AA inhibited ouabain-sensitive 86Rb uptake by >40%; the response to AA was attenuated by DBDD. We conclude that, in the PTs, 1) 20-HETE is a second messenger for ET-1 and 2) conversion of AA to 20-HETE is augmented when NOS is inhibited.


1966 ◽  
Vol 35 (3) ◽  
pp. 217-222 ◽  
Author(s):  
U. ZOR ◽  
H. AILABOUNI ◽  
F. G. SULMAN

SUMMARY The mechanism by which combined treatment with monoamine oxidase inhibitors and a corticosteroid reduces the weight of the accessory sex glands in intact rats by about one half has been studied. Phenelzine sulphate in combination with hydrocortisone acetate given for 30 days to ovariectomized rats reduced the pituitary stores of luteinizing hormone (LH) by 33%. Similar reductions in somatotrophic hormone, corticotrophin and thyroid-stimulating hormone content were found after comparable treatment, whereas luteotrophic hormone increased. The increase of weight of the seminal vesicles and prostate gland produced by human chorionic gonadotrophin could be partly antagonized by the simultaneous administration of mebanazine and dexamethasone, but the action of testosterone on these glands in castrated animals was not inhibited. Interference with the production and effectiveness of LH is therefore the most likely mode of action by which these drugs effect the reduction of the weight of the accessory sex glands.


1960 ◽  
Vol XXXIII (I) ◽  
pp. 73-80 ◽  
Author(s):  
J. C. Stucki ◽  
A. D. Forbes

ABSTRACT 17α-Hydroxyprogesterone acetate (AP) and 17α-hydroxyprogesterone caproate (HPC) were found to be incapable of maintaining pregnancy in ovariectomized rats when administered alone, even if administration of the drugs was started several days prior to surgery. Further studies with AP demonstrated that it could maintain pregnancy in the castrate rat when oestrone or testosterone propionate (TP) were concomitantly administered. The addition of TP to a regimen of concomitant AP and oestrone did not result in further improvement in the quality of pregnancy maintenance. TP and oestrone alone or together were incapable of maintaining pregnancy. Parturition could be delayed or prevented in intact rats with either progesterone or TP when administration of the steroids was started 3 days before the date of expected delivery. HPC and AP alone or with oestrone, and oestrone alone did not delay parturition when administration was begun late in pregnancy. Parturition was prevented when administration of AP was begun at least 11 days before expected delivery.


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