Proper nutritional status is critical for maintaining growth and metabolic function, playing an intimate role in neuroendocrine regulation. Leptin, the recently identified product of the obese gene, may very well be an integral signal which regulates neuroendocrine responses in times of food deprivation. The present study examines leptin's ability to regulate hormonal synthesis and secretion within the GRF-GH-IGF axis in the adult male rat during almost 3 days of fasting. Serum levels of GH and IGF-I were drastically suppressed by fasting. Daily leptin administration was able to fully prevent the fasting-induced fall in serum GH. Leptin failed to restore IGF-I to control levels, however, suggesting possible GH resistance. Fasting caused an insignificant increase in GH mRNA, while leptin injections significantly increased steady-state levels of this message. The GRF receptor (GRFr) message was not altered with fasting or leptin treatment. Leptin also exhibited effects at the hypothalamic level. Fasting induced a sharp fall in GRF mRNA expression and leptin injections partially prevented this fall. However, there were no observed changes in the hypothalamic GRF content. These results provide evidence that leptin may function as a neuromodulator of the GRF-GH-IGF axis communicating to this hormonal system the nutritional status of the animal.

ABSTRACT

Alphaxalone is considered the anaesthetic of choice in neuroendocrine reproductive studies in female rats, since it appears to have little, if any, effect on release of gonadotrophin-releasing hormone. There has been less study of the effects of this anaesthetic on the male reproductive neuroendocrine axis, however. Accordingly, the time-dependent effects of alphaxalone, as well as of urethane and ketamine, on the increased levels of LH in castrated rats were determined. Each anaesthetic was administered i.p. and each depressed LH levels significantly compared with those in castrated unanaesthetized rats killed by decapitation (controls). The effect of the anaesthetics was noted 15 min after administration and persisted at 30 and 60 min in animals anaesthetized with alphaxalone and urethane. Only in ketamine-anaesthetized animals did serum concentrations of LH finally rise to concentrations not significantly different from those in control rats. Thus alphaxalone, though useful in female neuroendocrine studies, is as profoundly disruptive as other anaesthetics on the male rat hypothalamic-pituitary reproductive unit.

J. Endocr. (1987) 115, 221–223

ABSTRACT

The effect of exposure to ethanol on hypothalamic LH-releasing hormone (LHRH) release in vivo was investigated in rats both acutely (i.p. injection) and after 3 days of administration, utilizing a permanent gastric cannula. In both designs, the animals were castrated before being given ethanol and, in both experiments, ethanol successfully lowered the post-castration LH rise compared with control castrated animals. In both the acutely and chronically treated groups, basal LHRH release was not impaired, despite the documented decrease in LH levels. Finally, stimulated LHRH release was investigated with depolarizing concentrations of potassium and, again, no change was noted between the hypothalamic release of this decapeptide in the ethanol-exposed compared with the ethanol-naive animals. Thus, ethanol failed to inhibit basal or stimulated LHRH secretion in the acutely and chronically treated animal. This lack of effect on LHRH occurred despite a concomitant lowering of serum concentrations of LH.

Journal of Endocrinology (1989) 121, 37–41

Abstract

Jurkat cells were used to study the immunomodulatory role of luteinizing hormone-releasing hormone (LHRH) in immune cells. The Jurkat cell, a human mature leukemic cell line, phenotypically resembles resting human T lymphocytes and has been widely used to study T cell physiology. The data from this study demonstrate that the Jurkat cell concentration of immunoreactive LHRH was 210 ± 36 pg/10⁶ cells and that of proLHRH was 188 ± 27 pg/10⁶ cells (means ± s.e.m.). The authenticity of this LHRH immunoreactivity is documented in two ways. First, both Jurkat LHRH and proLHRH immunoreactivity demonstrate dilutional parallelism with hypothalamic LHRH and proLHRH. Second, Jurkat lysates show LHRH bioactivity by releasing luteinizing hormone from rat anterior pituitary cells in culture. The presence of substantial amounts of LHRH in medium in which Jurkat cells were cultured for 72 h indicated that LHRH can be released from the cells. Using specific primers to exons 2 and 4 of the LHRH gene, we have found that Jurkat cells (like human T cells) express LHRH mRNA.

The LHRH agonist, des-Gly¹⁰,d-Trp⁶-LHRH ethylamide, significantly increases the proliferative activity of Jurkat cells, as assessed by tritiated thymidine incorporation, from 15 980 ± 1491 c.p.m. in controls to 28 934 ± 3395, 30 457 ± 3861 (P=0·05 vs control) or 35 299 ± 5586 c.p.m. (P<0·01 vs control) with 10⁻¹¹, 10⁻⁹ or 10⁻⁷ m agonist respectively. LHRH antagonist, [d-pGlu¹,d-Phe²,d-Trp^3,6]-LHRH, at a concentration of 10⁻⁸ m decreases Jurkat cell proliferative activity from 17 145 ± 526 c.p.m. in control medium to 10 653 ± 1323 c.p.m. (P=0·05). Co-incubation with the LHRH antagonist completely inhibits the proliferative stimulation induced by the LHRH agonist. Furthermore, applying monoclonal LHRH antibody to Jurkat cells inhibits the cell proliferative activity assessed by tritiated thymidine incorporation from 19 900 ± 2675 c.p.m. in controls to 15 680 ± 2254, 15 792 ± 1854 and 9700 ± 908 c.p.m. in media with 1:40, 1:20 and 1:10 dilution of purified antibody respectively (P<0·01, 1:10 dilution compared with control). In addition, the cAMP level in LHRH-stimulated Jurkat cells is decreased to 74, 27 and 57% of control levels after 15, 30 and 45 min respectively of exposure to 10⁻⁷ m LHRH agonist.

In summary, Jurkat cells produce, process and release immunoreactive and bioactive LHRH, as do normal human T cells. Endogenous and exogenous LHRH increase Jurkat cell proliferative activity, and cAMP may be involved in LHRH-induced Jurkat cell proliferation. The Jurkat cell may be a useful model with which to study the role of LHRH in human T cell function.

Journal of Endocrinology (1997) 153, 241–24