Estrogen Modulated Gonadotropin Release in Relation to Gonadotropin-Releasing-Hormone (GnRH) and Phorbol Ester (PMA) Actions in Superfused Rat Pituitary Cells*

Abstract

The involvement of protein kinase C (PKC) in GnRH action is still a matter of controversy. We have conducted a comparative study of LH and FSH release in response to GnRH and to phorbol ester myristate acetate (PMA), an activator of PKC, by rat pituitary cells maintained in culture. The effect of E2 pretreatment coupled or not with PKC depletion was also studied. Different kinetics in the response of LH and FSH to GnRH were observed, suggesting that the intracellular pathways involved in the release process of the two hormones were somewhat different. Moreover, PMA (10 nM) stimulated LH release greatly and FSH release only slightly. Intracellular PKC depletion, obtained by a prolonged treatment (18 h) of the cells with PMA (1 microM), produced different results according to the endocrine status of the pituitary cells. GnRH (10 nM)-induced LH release was significantly decreased in PKC-depleted cells from proestrous females. For PKC-depleted cells from OVX females, it was decreased significantly only when cells had been pretreated by E2. These results suggest that the modulation of LH secretion by E2 involves PKC activation. FSH release was poorly stimulated by PMA; but, under any conditions, PKC depletion did not affect GnRH-induced FSH release.

Estradiol Modulation of GNRH-Stimulated LH Release in Rat Anterior Pituitary Cells: Involvement of Dihydropyridine-Sensitive Calcium Channels

“…In a previous study we demon strated that PKC was implicated in the action of GnRH in cells pretreated with E2 [19,20]. In the present study, we demonstrated that the dihydropyridine-sensitive calcium channel antagonist PN 200-110 has an inhibiting effect on GnRH-stimulated LH release only in cells pretreated with E2.…”

“…Some authors, however, do not agree [ 18]. Recently our group has confirmed the implica tion of PKC in the action of GnRH, but this effect was related to treatment of the cells by E2 [19,20], It has also been demonstrated that binding of GnRH to its receptor results in an increase in intracellular calcium ([Ca2 + ]i), which initiates events such as hormone secretion [21,22], This has been confirmed more recently by several studies using fluorescence analysis on gonadotroph populations [23][24][25] or in single gonadotroph cells [26][27][28][29]. Also, GnRH-induced [Ca2 + ]i increase was greater when cells were treated by E2 and this increase was affected by extra cellular calcium [30], [Ca2 + ]i increase in gonadotroph cells occurs through two major mechanisms: (i) mobilization of Ca2+ from in tracellular bound stores [10,31] and (ii) the influx of cal cium [32] across the plasma membrane via the voltagesensitive calcium channels (VSCC).…”

Activation of the Novel Estrogen Receptor G Protein-Coupled Receptor 30 (GPR30) at the Plasma Membrane

“…Estrogen has long been known to trigger rapid biochemical signaling events, including activation of second-messenger cascades (13,(32)(33)(34) and lipid/protein kinases (35)(36)(37)(38). Similarly, other steroid hormones and their antihormones also elicit rapid actions (39 -42).…”

Role of PKC in the regulation of gonadotropin subunit mRNA levels: interaction with two native forms of gonadotropin-releasing hormone

“…The main objective of this study was to determine whether PKC is involved in GnRH-induced increases in GtH-␣, FSH-␤, and LH-␤ mRNA levels in goldfish pituitary cells. Although there are some exceptions (5,7,20,50), it is well established that PKC mediates GnRH effects on GtH secretion, as well as gene expression in mammalian model systems (33,39). In tilapia, PKC is involved in GnRH-stimulated LH release, as well as LH-␤ and GtH-␣, but not FSH-␤, transcription (19,49).…”