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Endometrial prostaglandins (PGs) and the PGE2/PGF2alpha ratio play an important role in regulating the estrous cycle and establishment of pregnancy. The enzymes downstream of cyclooxygenase-2 may determine the PGE2/PGF2alpha ratio in the porcine uterus. Thus, we have cloned porcine PGF synthase (PGFS) and microsomal PGE synthase-1 (mPGES-1) and characterized their expression in porcine endometrium during the estrous cycle and early pregnancy. PGFS and mPGES-1 amino acid sequences possessed a high degree (>67% and >77%, respectively) of identity with the other mammalian homologs. There was little modulation of mPGES-1 throughout the estrous cycle; however, PGFS expression was highly up-regulated in endometrium around the time of luteolysis. During early pregnancy, PGFS at the protein level showed a time-dependent increase (low on d 10-13, intermediate on d 14-23, and high on d 24-25). In pregnancy, expression of mPGES-1 was intermediate on d 10-11 and low on d 14-17 and then increased after d 22, reaching the maximum on d 24-25. Immunohistochemistry showed localization of PGFS and mPGES-1 proteins mainly in luminal and glandular epithelium. Concluding, the spatiotemporal expression of PGFS throughout the estrous cycle indicates an involvement of PGFS in regulating luteolysis in the pig. The comparison of endometrial PGFS and mPGES-1 expression on d 10-13 of the estrous cycle and pregnancy suggest a supportive role of these enzymes in determining the increase of uterine PGE2/PGF2alpha ratio during maternal recognition of pregnancy. Moreover, high expression of both PG synthases after initiation of implantation may indicate their significant role in placentation.

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TSH secretion from the anterior pituitary is mainly regulated by TRH and thyroid hormones. We hypothesized that in addition the pituitary itself could modulate TSH production by sensing its own TSH release, enabling fine-tuning of TSH secretion. For such an ultra-short loop control, the pituitary should contain a TSH receptor (TSH-R). To find evidence for this we screened a human pituitary complementary DNA library with a digoxigenin-labeled TSH-R probe and found 2 positive clones of 32,000 plaques. One clone was sequenced and found to be completely identical to the thyroid TSH-R. T SH IS THE major regulator of thyroid hormone synthesis and secretion. The production of TSH in the anterior pituitary is modulated by thyroid hormones via a classical negative feedback mechanism and by TRH from the hypothalamus by a positive feedforward mechanism. In concert with other circulating factors, such as dopamine, somatostatin, and some steroids, TRH and thyroid hormones are seen as the main determinants to maintain normal TSH secretion.We hypothesized that, in addition, TSH secretion might be fine-regulated in a short loop feedback at the pituitary level through the TSH receptor (TSH-R). This hypothesis was developed on two grounds. Firstly, because we were intrigued by the well known clinical observation that many patients with Graves' hyperthyroidism continue to show suppressed plasma TSH levels despite adequate antithyroid treatment, resulting in clinical euthyroidism and normal (or even low) plasma T 4 and T 3 levels (1, 2). In our experience this is less often seen in patients with other forms of hyperthyroidism. We wondered whether TSH-R-stimulating antibodies might suppress TSH secretion by direct action on the pituitary. If so, the pituitary should contain a TSH-R. Several reports have now demonstrated that the TSH-R is present at extrathyroidal sites. In the intestine, for example, it appears to be involved in a local paracrine network of hormonal regulation of T cell homeostasis in response to locally produced TSH (3).Secondly, we hypothesized that it would be more efficient for the fine-tuning of TSH secretion (i.e. to keep TSH plasma levels within a certain range) if the pituitary was able to measure and regulate its own TSH production, in analogy to modern heating boilers, which regulate their heat production through built-in temperature sensors in addition to the room thermostat.A pituitary TSH-R might be involved in TSH secretion at the pituitary level in an autocrine fashion via a TSH-R on the thyrotroph itself. Alternatively, it might be mediated in a paracrine fashion through another cell type. A likely candidate for this is the folliculo-stellate (FS) cell (4), which is known to produce various cytokines and other regulatory factors, mostly notably IL-6 (5, 6).To test our hypothesis, we set out to study the presence and cellular localization of the TSH-R in the human anterior pituitary using several, independent methods aimed at finding both TSH-R messenger ribonucleic acid (mRNA) and protein. Ma...