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

Abstract

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.

The Use of Flufenamate and Forskolin to Evaluate the Role of cAMP in Gonadotropin‐Releasing Hormone‐Stimulated Luteinizing Hormone Secretion from Pituitaries of Ovariectomized Rats

“…As mentioned in the Introduction, the GnRH-stimulated, protein synthesis-dependent component of LH secretion from pituitaries of ovariectomized rats is attenuated when compared to intact females (Baldwin et al 1983). Oestradiol was shown to affect cAMP production (Tang et al 1982), CAMP-dependent protein kinase (PKA) activity, cAMP binding (Tang & Tang 1983), and the ability of the nucleotide to stimulate LH secretion (Kolp et al 1991). Consequently, ovariectomy and the resultant decrease in circulating oestradiol concentrations could conceivably result in decrease cAMP production, decreased cAMP binding and decreased PKA activity.…”