Inhibition of salmon calcitonin on secretion of progesterone  and GnRH-stimulated pituitary luteinizing hormone

The effects of salmon calcitonin (sCT) on the production of progesterone and secretion of luteinizing hormone (LH) were examined in female rats. Diestrous rats were intravenously injected with saline, sCT, human chorionic gonadotropin (hCG), or hCG plus sCT. Ovariectomized (Ovx) rats were injected with saline or sCT. In the in vitro experiments, granulosa cells and anterior pituitary glands (APs) were incubated with the tested drugs. Plasma LH levels of Ovx rats were reduced by sCT injection. Administration of sCT decreased the basal and hCG-stimulated progesterone release in vivo and in vitro. 8-Bromo-cAMP dose dependently increased progesterone production but did not alter the inhibitory effect of sCT. H-89 did not potentiate the inhibitory effect of sCT. Higher doses of 25-hydroxycholesterol and pregnenolone stimulated progesterone production and diminished the inhibitory effects of sCT. sCT did not decrease basal release of LH by APs, but pretreatment of sCT decreased gonadotropin-releasing hormone (GnRH)-stimulated LH secretion. These results suggested that sCT inhibits progesterone production in rats by preventing the stimulatory effect of GnRH on LH release in rat APs and acting directly on ovarian granulosa cells to decrease the activities of post-cAMP pathway and steroidogenic enzymes.

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Inhibition of LH-stimulated cyclic AMP formation in pre-ovulatory rat granulosa cells by follicular fluid

Acta Endocrinologica ◽

10.1530/acta.0.0950084 ◽

1980 ◽

Vol 95 (1) ◽

pp. 84-89 ◽

Cited By ~ 2

Author(s):

Knut Nordenström ◽

Anita Sjögren ◽

Lars Hamberger

Keyword(s):

Granulosa Cells ◽

Follicular Fluid ◽

Phosphodiesterase Inhibitor ◽

Inhibitory Effect ◽

Female Rats ◽

Bicarbonate Buffer ◽

Ovulatory Follicles

Abstract. Immature female rats were injected sc with a single dose of PMSG to induce growth and maturation of ovarian follicles. In the morning of prooestrus the rats were given a single ip injection of LH (10 μg/rat) or 0.154 m NaCl, 2 h prior to sacrifice. Granulosa cells were isolated from the pre-ovulatory follicles and incubated in Krebs bicarbonate buffer, for 1 h with or without in vitro addition of various test substances. Following incubation the amounts of cAMP in tissue plus medium were determined. It was found that the isolated granulosa cells exposed to LH in vivo responded to the addition of LH in vitro with a production of high amounts of cAMP, i.e. these cells were not refractory to LH stimulation and in fact responded better than granulosa cells isolated from ovaries not exposed to LH in vivo. The addition to the incubation medium of follicular fluid (FFl) obtained from pre-ovulatory follicles decreased the effect of LH in vitro when added at a final concentration of 1% and completely abolished it at a concentration of 3%. Removal of steroids from the FFl did not influence the inhibitory effect and the addition of a phosphodiesterase inhibitor (IBMX) in vitro did not alter the results in principle. These results point to the existence of a factor in the FF1 which interacts with the sensitivity of the isolated preovulatory granulosa cells to repeated exposures to LH. Characterization of this factor is subject to further investigations.

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Homologous and heterologous regulation of somatostatin-binding sites on chicken adenohypophysial membranes

Journal of Endocrinology ◽

10.1677/joe.0.1270417 ◽

1990 ◽

Vol 127 (3) ◽

pp. 417-425 ◽

Cited By ~ 4

Author(s):

S. Harvey ◽

J. S. Baidwan ◽

D. Attardo

Keyword(s):

Pituitary Gland ◽

Binding Sites ◽

Recombinant Dna ◽

Inhibitory Effect ◽

Partial Recovery ◽

Caudal Lobe ◽

Direct Inhibitory Effect ◽

Pituitary Glands

ABSTRACT Binding of 125I-labelled [Tyr1]-somatostatin (125I-[Tyr1]-SRIF) to pituitary caudal lobe membranes was suppressed in immature chickens 1 and 2 h after i.v. administration of unlabelled SRIF at concentrations of 1–100 μg/kg. In-vitro preincubation of chicken pituitary glands for 0·5–4·0 h with 0·1 μmol SRIF/l similarly reduced the binding of 125I-[Tyr1]-SRIF to caudal lobe membrane preparations. After a 4-h incubation in 0·1 mmol SRIF/l, the withdrawal of SRIF from the incubation media was accompanied 4 h later by a partial recovery in the binding of 125I-[Tyr1]-SRIF to pituitary membranes. Passive immunoneutralization of endogenous SRIF resulted in a prompt (within 1 h) and sustained (for at least 24 h) suppression of 125I-[Tyr1]-SRIF binding to pituitary membranes. The i.m. administration of cysteamine (300 mg/kg) to 12-week-old birds depleted hypothalamic SRIF stores and decreased the density of 125I-[Tyr1]-SRIF-binding sites in the caudal and cephalic lobes of the chicken pituitary gland. The reduction in SRIF content and in SRIF-binding sites occurred within 1 h of cysteamine administration and was maintained for at least 24 h. In 6-week-old birds, cysteamine (300 mg/kg) administration suppressed pituitary binding of 125I-[Tyr1]-SRIF for at least 5 days. Circulati concentrations of GH were markedly decreased 1 and 4 h after cysteamine injection, but not after 24 h. Pituitary binding sites for 125I-[Tyr1]-SRIF were not affected by pretreatment of pituitary glands for 2–12 h in vitro with thyroxine or oestradiol-17β (1 nmol/l–10 μmol/l) or with ovine GH or recombinant DNA-derived chicken GH (1–100 μg/ml in vitro and 100–1000 μg/kg in vivo). Ovine prolactin, at concentrations of 1–100 μg/ml was also without effect on 125I-[Tyr1]-SRIF binding to pituitary membranes following a 2- or 4-h incubation with pituitary glands. Pituitary binding sites for 125I-[Tyr1]-SRIF were, however, increased after a 24-h incubation with 1 μmol tri-iodothyronine (T3)/l in vitro and 4 and 24 h after the administration of T3 (100–1000 μg/kg) in vivo. Although T3 had no direct inhibitory effect on 125I-[Tyr1]-SRIF binding to pituitary membranes, binding was suppressed 1 and 2 h after the in-vivo administration of T3 at concentrations of 100–1000 μg/kg. These results therefore demonstrate homologous and heterologous regulation of SRIF-binding sites in the chicken pituitary gland. Journal of Endocrinology (1990) 127, 417–425

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Dichotomic action of glucocorticoids on growth hormone secretion

Acta Endocrinologica ◽

10.1530/acta.0.1160165 ◽

1987 ◽

Vol 116 (2) ◽

pp. 165-171 ◽

Cited By ~ 48

Author(s):

Koji Nakagawa ◽

Tatsuya Ishizuka ◽

Takao Obara ◽

Miyao Matsubara ◽

Kazumasa Akikawa

Keyword(s):

Hormone Secretion ◽

Growth Hormone Secretion ◽

Inhibitory Effect ◽

Female Rats ◽

Pituitary Cells ◽

Gh Secretion ◽

Normal Rat ◽

Rat Pituitary Cells

Abstract. The mechanism of apparently discrepant actions of glucocorticoids (GC) on GH secretion, in vivo suppression and in vitro potentiation, was studied in rats. Dexamethasone (Dex), at the concentration of 50 nmol/l, Potentiated basal and GHRH-stimulated GH release from monolayer culture of normal rat pituitary cells in 48 h. On the other hand, in vivo administration of Dex, 165 μg daily for 3 days, consistently suppressed serum GH levels in female rats. In these rats, the hypothalamic content of immunoreactive (IR) SRIH was significantly increased, whereas that of IR-GHRH was significantly decreased in comparison with the untreated rats. Bioassayable GH-releasing activity was also lower in Dex-treated rats. These findings indicate that the suppressing effect of GC on GH release in vivo is, at least partially, due to the increase in hypothalamic SRIH release and probably also to the decrease in GHRH release, and these effects surpass the potentiating effect of GC on GH release at the pituitary level, resulting in a net inhibitory effect in vivo.

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Galanin Enhancement of Gonadotropin-Releasing Hormone-Stimulated Luteinizing Hormone Secretion in Female Rats Is Estrogen Dependent

Endocrinology ◽

10.1210/en.2002-220855 ◽

2003 ◽

Vol 144 (2) ◽

pp. 484-490 ◽

Cited By ~ 22

Author(s):

Cynthia L. Splett ◽

Joseph R. Scheffen ◽

Joshua A. Desotelle ◽

Vicky Plamann ◽

Angela C. Bauer-Dantoin

Keyword(s):

Luteinizing Hormone ◽

Hormone Secretion ◽

Gonadotropin Releasing Hormone ◽

Gonadal Steroids ◽

Female Rats ◽

Luteinizing Hormone Secretion ◽

Ovx Rats ◽

Lh Secretion ◽

Lines Of Evidence

The hypothalamic peptide GnRH is the primary neuroendocrine signal regulating pituitary LH in females. The neuropeptide galanin is cosecreted with GnRH from hypothalamic neurons, and in vitro studies have demonstrated that galanin can act at the level of the pituitary to directly stimulate LH secretion and also augment GnRH-stimulated LH secretion. Several lines of evidence have suggested that the hypophysiotropic effects of galanin are important for the generation of preovulatory LH surges. To determine whether the pituitary actions of galanin are enhanced by the preovulatory steroidal milieu, LH responses to galanin administration (with or without GnRH) were examined in: 1) ovariectomized (OVX); 2) OVX, estrogen (E)-primed; and 3) OVX, E- and progesterone-treated female rats. Results from the study indicate that galanin enhances GnRH-stimulated LH secretion only in the presence of E (in OVX, E-primed, or E- and progesterone-treated rats). Galanin alone does not directly stimulate LH secretion under any of the steroid conditions examined. In the absence of gonadal steroids (OVX rats), galanin inhibits GnRH-stimulated LH secretion. These findings suggest that the primary pituitary effect of galanin is to modulate GnRH-stimulated LH secretion, and that the potentiating effects of galanin occur only in the presence of E.

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Follicle-Stimulating Hormone and Luteinizing Hormone/Chorionic Gonadotropin Stimulation of Vascular Endothelial Growth Factor Production by Macaque Granulosa Cells from Pre- and Periovulatory Follicles1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.82.7.4169 ◽

1997 ◽

Vol 82 (7) ◽

pp. 2135-2142

Author(s):

Lane K. Christenson ◽

Richard L. Stouffer

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Granulosa Cells ◽

Dependent Manner ◽

Vascular Endothelial ◽

Progesterone Production ◽

Endothelial Growth Factor ◽

In Vitro Treatment

Granulosa cells in the ovulatory follicle express messenger ribonucleic acid encoding vascular endothelial growth factor (VEGF), an agent that may mediate the neovascularization of the developing corpus luteum, but it is not known whether luteinizing granulosa cells synthesize and secrete VEGF during the periovulatory interval. Studies were designed to evaluate the effects of an in vivo gonadotropin surge on VEGF production by macaque granulosa cells (study 1) and to test the hypothesis that gonadotropins act directly on granulosa cells to regulate VEGF production (study 2). Monkeys received a regimen of exogenous gonadotropins to promote the development of multiple preovulatory follicles. Nonluteinized granulosa cells (i.e. preovulatory; NLGC) and luteinized granulosa cells (i.e. periovulatory; LGC) were aspirated from follicles before and 27 h after an ovulatory gonadotropin bolus, respectively. Cells were either incubated for 24 h in medium with or without 100 ng/mL hCG (study 1) or cultured for 6 days in medium with or without 100 ng/mL hCG or 0.1, 1, 10, and 100 ng/mL of recombinant human LH (r-hLH) or r-hFSH (study 2). Culture medium was assayed for VEGF and progesterone. In study 1, LGC produced 8-fold greater levels of VEGF than NLGC (899 ± 471 vs. 111 ± 26 pg/mL, mean ± sem; P < 0.05). In vitro treatment with hCG increased (P < 0.05) VEGF production by NLGC to levels that were not different from the LGC incubated under control conditions. In vivo bolus doses of r-hCG (100 and 1000 IU) and r-hFSH (2500 IU) were equally effective in elevating granulosa cell VEGF production. In study 2, in vitro treatment with r-hFSH, r-hLH, and hCG markedly increased (P< 0.05) VEGF and progesterone production by the NLGC in a dose- and time-dependent manner. By comparison, the three gonadotropins (100 ng/mL dose) only modestly increased VEGF and progesterone production by LGC. These experiments demonstrate a novel role for the midcycle surge of gonadotropin (LH/CG or FSH) in primates to promote VEGF production by granulosa cells in the periovulatory follicle. Further, the data demonstrate that FSH-like as well as LH-like gonadotropins directly stimulate VEGF synthesis by granulosa cells.

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GONADOTROPHIN RELEASE IN VITRO, IN THE PRESENCE AND ABSENCE OF LUTEINIZING HORMONE RELEASING HORMONE, BY PITUITARY GLANDS FROM OVARIECTOMIZED AND SHAM-OPERATED IMMATURE FEMALE RATS OF VARIOUS AGES

Journal of Endocrinology ◽

10.1677/joe.0.0880375 ◽

1981 ◽

Vol 88 (3) ◽

pp. 375-379

Author(s):

J. DULLAART

Keyword(s):

Female Rats ◽

Ovariectomized Rats ◽

Immature Female ◽

Releasing Hormone ◽

Incubation Experiments ◽

Immature Rats ◽

Pituitary Glands ◽

Lh Releasing Hormone

Hemipituitary glands of immature female rats, aged 10, 15, 20, 25, 30 and 35 days and either ovariectomized or sham-operated 5 days earlier, were incubated for 2 h in vitro with or without LH releasing hormone. Concentrations of LH and FSH were determined at the end of the incubations in the incubation media and in the hemipituitary glands, and also in the sera collected at the beginning of the incubation experiments. Results showed that in many instances gonadotrophin release was higher after incubation of glands of ovariectomized rats than with glands of control animals. However, these effects of ovariectomy were much smaller than those observed in vivo and were generally absent in rats of less than 20 days of age. It was concluded that ovariectomy may change the secretory characteristics of the gonadotrophic cells of immature rats but that such changes were largely restricted to immature rats older than 20 days.

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Release and synthesis of FSH by pituitary glands of female rats in vitro

Acta Endocrinologica ◽

10.1530/acta.0.1000499 ◽

1982 ◽

Vol 100 (4) ◽

pp. 499-503 ◽

Cited By ~ 2

Author(s):

A. A. J. Jenner ◽

J. de Koning ◽

G. P. van Rees

Keyword(s):

Protein Synthesis ◽

Slow Rate ◽

Female Rats ◽

Intact Female ◽

Ovx Rats ◽

Basal Release ◽

Pituitary Glands ◽

Independent Synthesis ◽

Intact Rats

Abstract. Anterior hemi-pituitary glands from intact female and ovariectomized (OVX) rats were incubated with or without a maximally effective dose of LRH. During an 8 h incubation, LRH-stimulated release of FSH by pituitary glands from intact rats was biphasic: an initial slow rate of release and, from 2 to 8 h, an enhanced rate of release. Basal release was low up to 4 h, after which a marked increase of the rate of release was measured: from 6 to 8 h there was no difference between the rates of basal and LRH-stimulated release. Basal and LRH-stimulated release of FSH by pituitary glands from OVX rats were high and approximately constant during an 8 h incubation. Both basal and LRH-stimulated release by glands from intact as well as OVX rats were protein synthesis dependent. During the incubations an LRH-independent synthesis of FSH was measured. The results suggest that this synthesis is involved, either directly or indirectly, in increasing the rate of basal release of FSH after 4 h. A comparison of release and synthesis of FSH with those of LH reveals characteristic differences.

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The effect of the somatostatin analog SMS 201-995 on normal growth hormone secretion in the rat.

Acta Endocrinologica ◽

10.1530/acta.0.1150196 ◽

1987 ◽

Vol 115 (2) ◽

pp. 196-202 ◽

Cited By ~ 8

Author(s):

Steven W. J. Lamberts ◽

Theo Verleun ◽

Joke M. Zuiderwijk ◽

Rob Oosterom

Keyword(s):

Dopamine Agonist ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Inhibitory Effect ◽

Somatostatin Analog ◽

Pituitary Tumours ◽

Pituitary Glands

Abstract. The somatostatin analog SMS 201-995 was recently shown to be effective in suppressing GH secretion and in causing tumour shrinkage in patients with GH-secreting pituitary tumours. In this respect, the action of SMS 201-995 seems similar to that of the dopamine-agonist bromocriptine in patients with PRL-secreting pituitary tumours. In the present study we compared the respective effects of SMS 201-995 and bromocriptine on normal rat GH and PRL release in vivo and in vitro. Both in vitro and in vivo, repeated administration of SMS for up till 6 days suppressed circulating GH concentrations, and the ability of the pituitary glands to release GH in vitro. A dose-dependent diminution occurred of the total pituitary GH content in rats treated in vivo with SMS 201-995 for 4–6 days. During short-term in vitro incubation for only 4 h, the total amount of GH measured in the medium + gland was also diminished. Chronic administration with SMS 201-995 (2 μg/kg twice daily for 15 days), however, resulted in a complete desensitization of its inhibitory effect on GH synthesis and release. In similar experiments it was shown that the dopamine agonist bromocriptine affects normal PRL secretion in a different manner. Both in vitro (10 nmol/l) and in vivo administration for 6 days (0.2 mg/kg twice daily) greatly inhibited circulating PRL levels and the ability of the pituitary glands to release PRL in vitro. This is, however, in all instances accompanied by an accumulation of PRL within the pituitary gland. Long-term bromocriptine administration (0.2 mg/kg twice daily for 15 days) inhibited PRL secretion, and finally also a decrease in the total pituitary PRL content was observed. It is shown in this study that SMS 201-995 and bromocriptine affect hormone release by normal pituitary glands in a different manner. SMS 201-995 acutely inhibits GH release and diminishes within a few hours of exposure also the GH content in normal cells by a powerful inhibition of GH synthesis and/or an increase in intracellular degradation of GH. Bromocriptine, however, exerts primarily an inhibitory effect on PRL release, whereas an inhibition of synthesis and/or degradation of intracellular PRL is evident only after long-term exposure to the drug.

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