Background: Kisspeptin and its cognate receptor GPR54 are the central driving forces in the hypothalamus-pituitary-gonadal axis essential for sexual maturation and reproduction. Kisspeptin/GPR54 signalling stimulates gonadotropin-releasing hormone (GnRH) neurones and induces pulsatile GnRH release. The molecular signalling pathway by which kisspeptin stimulates GnRH neurones is currently under investigation. Methods: Primary GnRH neurones were isolated from young adult rats and loaded with the calcium indicator Fura Red. Cytosolic calcium was measured while the cells were stimulated with kisspeptin. Results: GnRH neurones show a maintained increase of cytosolic calcium upon stimulation with 100 nM kisspeptin-10. The calcium elevation was inhibited 30% by 1 µM tetrodotoxin, a voltage-gated sodium channel blocker, and 76% by 30 µM SKF96365, an inhibitor of receptor-mediated calcium entry. Furthermore, removal of extracellular calcium completely abolished the kisspeptin-induced calcium elevation. Conclusion: Our results suggest that the major part of the kisspeptin-evoked calcium signal is generated by an action potential-independent calcium influx, possibly through channels of the classical transient receptor potential type, with an additional influx through voltage-gated calcium channels activated by sodium action potentials.

T4-, T3- and reverse-T3 concentrations were measured in the sera of 365 subjects beyond the age of 65 in order to evaluate if the decrease of serum T3 frequently observed in old age can be attributed to old age per se or to concomitant nonthyroidal disease. The results obtained from a carefully selected healthy group of elderly people show that 1) total and free T3 levels are lower in senescence but well within the range for euthyroidism in younger healty controls;2) the decrease of serum T3 is more pronounced and occurs earlier in healthy old males than in females, so that for subjects over the age of 75, the upper limit for euthyroidism has to be adjusted by 10% in women and by 20% in men; and 3) there is no low T3 syndrome characterized by decreased serum T3 and increased serum reverse T3, solely due to old age. Turnover kinetics have shown the daily production of T4 and T3 in old age to decrease by 20 micrograms and 10 micrograms, respectively, and an increased T3 metabolic clearance not to account for the reduction of serum T3 concentrations. Combined stimulation tests with TSH and TRH showed that the functional reserve of the thyroid gland to produce T3 is maintained in old age. The first step in the sequence of events may be seen in an impairment of TSH secretion leading to an adaptation of the amount of thyroid hormones to a reduced mass of metabolically active body tissue in old age.

Free Triiodothyronine (T3)-and Thyroxine (T4) Serum Levels in Old Age 239 Due to the ubiquitous distribution of adipose tissue and the substantial insulin degrading activity observed, it would appear that this tissue may play an important role in insulin turnover in the body. References