Nitric oxide inhibits prolactin secretion in pituitary cells downstream of voltage-gated calcium influx.
The coupling between nitric oxide (NO)-cGMP signaling pathway and prolactin (PRL) release in pituitary lactotrophs has been established previously. However, the messenger that mediates the action of this signaling pathway on hormone secretion and the secretory mechanism affected, calcium dependent or independent, have not been identified. In cultured pituitary cells, basal PRL release was controlled by spontaneous voltage-gated calcium influx and was further enhanced by depolarization of cells and stimulation with TRH. Inhibition of constitutively expressed neuronal NO synthase decreased NO and cGMP levels and increased basal PRL release. The addition of a slowly releasable NO donor increased cGMP levels and inhibited basal PRL release in a time-dependent manner. Expression of inducible NO synthase also increased NO and cGMP levels and inhibited basal, depolarization-induced, and TRH-induced PRL release, whereas inhibition of this enzyme decreased NO and cGMP production and recovered PRL release. None of these treatments affected spontaneous and stimulated voltage-gated calcium influx. At basal NO levels, the addition of permeable cGMP analogs did not inhibit PRL secretion. At elevated NO levels, inhibition of cGMP production and facilitation of its degradation did not reverse inhibited PRL secretion. These experiments indicate that NO inhibits calcium-dependent PRL secretion in a cGMP-independent manner and downstream of voltage-gated calcium influx.
Andric
Silvana A
SA
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892-4510, USA.
Gonzalez-Iglesias
Arturo E
AE
Van Goor
Fredrick
F
Tomić
Melanija
M
Stojilkovic
Stanko S
SS
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D018408:Patch-Clamp Techniques; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D015220:Calcium Channels; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; D006152:Cyclic GMP; D002118:Calcium