Phebe K. Thompson

At least two hypothalamic peptides, corticotropin releasing hormone (CRH) and vasopressin (VP), are important in regulating adrenocorticotropin (ACTH) release from the anterior pituitary. Both are secreted in a pulsatile manner and stimulate ACTH secretion by interacting with G protein-coupled receptors (GPCRs), namely the type 1 CRH receptor and V1b receptor, respectively. Repeated or prolonged stimulation with either peptide can cause reduced ACTH responsiveness or desensitisation, both in vivo and in vitro. Desensitisation of perifused sheep anterior pituitary cells to VP was found to be rapid and occurred following treatment with 5 nM VP for 5 min. This is within the range of concentrations and durations of VP pulses seen in sheep portal blood during acute stress. In contrast, significant desensitisation of the ACTH response to CRH required pre-treatment for longer than 25 min with a CRH concentration of 1 nM, suggesting that endogenous pulses may not elicit desensitisation. Although rapid GPCR desensitisation involves uncoupling of receptors from their G proteins, commonly mediated by receptor phosphorylation, and internalisation of receptors, desensitisation of neither the CRH nor VP receptor was mediated by PKA or PKC, respectively. Desensitisation of the response to VP was found to be dependent upon receptor internalisation, and resensitisation could be delayed by treatment with a protein phosphatase 2B inhibitor. The rapid kinetics of desensitisation of the ACTH response to VP suggest that this process is important in regulating the response to acute rather than chronic stress. If, as has been suggested, CRH acts in a permissive way to set corticotrope gain, desensitisation to CRH could also be important in long term regulation of ACTH secretion.

Basal metabolic rates were determined with the Roth-Benedict apparatus, using Aub-DuBois stndards.

Clinical findings, beginning with those of Cushing and his co-workers (1) and of Aschner (2) about 25 years ago, and the more recent experimental results of Zondek (3), Smith (4), Smith and Engle (5), Evans and Long (6), Moore and co-workers (7), in animals, furnish clear cut evidence of the effect of the anterior lobe of the pituitary on the growth and function of the gonads. While extensive observations on animals were being carried out by various investigators on the effects of the pituitary, Aschheim and Zondek (8) noted the presence in the urine of pregnant women of a substance that stimulated the sex glands. Shortly afterward, the production of genital growth and testicular descent with this material was reported by Schapiro (9) in a large percentage of boys and young men with hypogenitalism and cryptorchidism. Since then several reports have appeared, most of which give high percentages of successful results. To some surgeons familiar with the finding at operation of anatomical factors making descent difficult or impossible, many of these reports appeared enthusiastic. It therefore seemed desirable to make a critical study of the problem by a group of observers, one of whom should be a surgeon of wide and extensive experience in this field (10, 11, 12). Embryological considerations. The testis appears about the 5th week as the genital ridge or mass. There are differences of opinion concerning some of the details of its development. The consensus among embryologists is that the cells of the distal portion of the mass proliferate, while those of the proximal end atrophy; at the same time the fetus grows so that the testis appears to aescend to the level of the inguinal ring, which is being prepared for it.