Luteinizing Hormone Secretion Is Enhanced by Pertussis Toxin, Cholera Toxin, and Forskolin

Cronin, Michael J.; Evans, William S.; Hewlett, Erik L.; Rogol, Alan D.; Thorner, Michael O.

doi:10.1159/000123535

Cited by 12 publications

(2 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When applied to pituitary cell cultures, it pro motes a massive synthesis of intracellular cAM P and an in tense output of the nucleotide to the medium. Our results accord well with the data recently reported by Cronin et al [4], RMI 12,330 A inhibits the adenylate cyclase activity within plated cells as well as within a pituitary homogenate. On the contrary, SQ 22,536 which inhibits the cyclase in an acellular system is obviously unable to block the cyclic nu cleotide synthesis within cultured cells.…”

Section: Discussionsupporting

confidence: 93%

Luteinizing Hormone and Prolactin Release by Cultured Pituitary Cells and by Gonadotrope- and Lactotrope-Enriched Populations in the Presence of Modulators of Adenylate Cyclase

Defontaine¹,

Monti

Duval

1985

Neuroendocrinology

View full text Add to dashboard Cite

The effects of 3 compounds previously known to alter the adenylate cyclase activity in various tissues were tested on rat pituitary. Forskolin increased while RMI 12,330 A and SQ 22,536 decreased enzyme activity of pituitary homogenates. Forskolin (10^–5M) promoted in cultured cells a massive synthesis of cyclic adenosine monophosphate (cAMP) and intense output of the nucleotide in the medium; at the same concentration, RMI 12,330 A decreased the cell content of cAMP while release was unaffected, and SQ 22,536 exerted no effect on the cyclic nucleotide amount of both cell and medium. The basal release of plated total cells or enriched gonadotropes was slightly stimulated by forskolin (10^–7–10^–5M) though the level of stimulation never attained the one produced by 10^–7M luteinizing hormone-releasing hormone (LHRH); it was affected neither by RMI 12,330 A (10^–7–10^–5M) nor by SQ 22,536 (10^–7–10^–4M). The LHRH-stimulating effect was slightly amplified during the 1st h (sensitivity response of cells) by low concentrations of forskolin (10^–7 and 10^–6M) but the overall luteinizing hormone (LH) release after 4 h of incubation (capacity response of cells) was unmodified. Higher concentrations of the diterpene inhibited the LHRH effect as seen with total cells and with enriched gonadotropes. RMI 12,330 A at 10^⁵M significantly inhibited the LHRH-promoted LH release from total cells and from gonadotropes but a higher concentration (10^–4M) promoted a large unspecific release that masked the LHRH effect. SQ 22,536 never modified the cell response to LHRH, whatever the drug concentration. We thus conclude that LH release is partly cAMP dependent, the cyclic nucleotide acting during the very early phase of LHRH action (on the readily releasable LH pool, i.e. sensitivity response) but exerting no effect during the 2nd step (mobilization of LH stores, i.e. capacity response). Forskolin (10^–7 10^–5M) stimulated prolactin (PRL) release, but it was unable to overcome the dopamine-(DA-)inhibiting effect though the adenylate cyclase was stimulated by 10^–6M of the diterpene in the presence of 10^⁷ M DA. 10^–5M of RMI 12,330 A inhibited PRL release as efficiently as 10^–7M DA did. SQ 22,536 exerted no effect, whatever the drug concentration. These results confirm the participation of the cAMP-generating system in PRL release; however, activation of the adenylate cyclase is not sufficient to stimulate hormone release once other membrane events are blocked.

show abstract

Section: Discussionsupporting

confidence: 93%

Luteinizing Hormone and Prolactin Release by Cultured Pituitary Cells and by Gonadotrope- and Lactotrope-Enriched Populations in the Presence of Modulators of Adenylate Cyclase

Defontaine¹,

Monti

Duval

1985

Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…Employing cholera toxin, forskolin and extracytoplasmic adenylate cyclase obtained from the Bordetellci pertussis organism, we found that both basal and GnRH-stimulated LH release is enhanced in the presence of increased cAMP production [26,27], In subsequent studies using cells in a continuous perifusion system, we found that the release of LH is delayed and gradual following application of probes known to enhance cAMP production immediately in contrast to the brisk, immediate rise which occurs in response to GnRH [15]. Taken together, these investigations confirmed a relationship between cAMP and LH secretion separate from any effect on the GnRH receptor and suggested that the failure of some investigators to document this relationship may be at tributable to the experimental time course required to detect the cAMP effect.…”

Section: Discussionmentioning

confidence: 96%

Forskolin-Associated Luteinizing Hormone Release by Rat Anterior Pituitary Glands: Effects of Castration and Estradiol Replacement

1991

View full text Add to dashboard Cite

We have previously shown that the diterpene forskolin, a compound which increases intracellular cyclic AMP (cAMP), causes a concentration-dependent release of luteinizing hormone (LH) by continuously perifused anterior pituitary cells from female rats. To test the hypothesis that cAMP-associated LH release is an estrogen-dependent process, we first compared concentration-response relationships between forskolin and both cAMP production and LH secretion by tissue obtained from intact female, intact male and ovariectomized (OVX) rats. Anterior pituitary fragments were perifused with medium alone or medium plus several concentrations of forskolin for 4 h. All three groups demonstrated concentration-dependent cAMP production in response to forskolin. However, while a concentration-dependent release of LH by forskolin was confirmed in pituitary fragments from intact female rats, no such relationship could be identified for tissue from OVX or male rats. Pituitary fragments from OVX rats administered estradiol via silastic capsule for 48 h were next challenged with 3 µM forskolin. In response to this submaximal concentration of the diterpene, a brisk increase in LH secretion was observed. These results demonstrate that, although forskolin stimulates the production of cAMP in intact male, intact female and OVX animals, an associated release of LH can be documented only in the intact female group. These findings, together with the observation that administration of estrogen appears to restore forskolin-associated LH secretion in OVX animals, suggest that estrogen may play a key role in the stimulation of LH release by cAMP.

show abstract

Evidence for Sex Differences in GnRH Receptors and Mechanism of Action

Mitchell

Ogier

Johnson

et al. 1986

Neuroendocrine Molecular Biology

View full text Add to dashboard Cite

Luteinizing Hormone Secretion Is Enhanced by Pertussis Toxin, Cholera Toxin, and Forskolin

Cited by 12 publications

References 6 publications

Luteinizing Hormone and Prolactin Release by Cultured Pituitary Cells and by Gonadotrope- and Lactotrope-Enriched Populations in the Presence of Modulators of Adenylate Cyclase

Luteinizing Hormone and Prolactin Release by Cultured Pituitary Cells and by Gonadotrope- and Lactotrope-Enriched Populations in the Presence of Modulators of Adenylate Cyclase

Forskolin-Associated Luteinizing Hormone Release by Rat Anterior Pituitary Glands: Effects of Castration and Estradiol Replacement

Evidence for Sex Differences in GnRH Receptors and Mechanism of Action

Contact Info

Product

Resources

About