Stimulation der TSH-Sekretion durch TRF-Belastung bei hypothalamischen und hypophysären Krankheitsbildern

1. Die Antworten der Serum-TSH-Spiegel (Thyreoidea-stimulierendes Hormon) auf TRF-Injektion (Thyrotropin Releasing Factor) bei 8 Normalpersonen und 37 z. T. zweimal untersuchten Patienten mit hypophysärer oder hypothalamischer Erkrankung werden mitgeteilt. 2. Hypophysektomierte Patienten mit intrasellären Tumoren (N=12) zeigten keine oder nur subnormale Anstiege der TSH-Spiegel. 3. Von 9 präoperativ untersuchten Patienten mit intrasellärem HVL-Adenom hatten 3 eine sekundäre Hypothyreose. Diese 3 reagierten dennoch mit einem normalen Anstieg der TSH-Spiegel. Dieser Befund schränkt die diagnostische Wertigkeit der TRF-Belastung zur Differenzierung hypophysärer und hypothalamischer sekundärer Hypothyreosen ein. Die 6 euthyreoten Patienten dieser Gruppe zeigten erwartungsgemäß einen normalen TSH-Anstieg. 4. Bei den Patienten mit sekundärer Hypothyreose bei suprasellärem Tumor oder hypothalamischer Erkrankung (N=7) fand sich mit einer Ausnahme ein normaler oder ein erhöhter TSH-Anstieg. Die Bedeutung des Ausschlusses einer primären Hypothyreose wurde dargestellt, da diese Erkrankung ebenfalls durch erhöhte TSH-Anstiege bei TRF-Belastung charakterisiert ist. 5. Je ein Patient aus der Gruppe der aktiven (N=7) und der behandelten (N=6) Akromegalie zeigten einen nicht auf eine primäre Hypothyreose zurückführbaren erhöhen TSH-Anstieg, dessen Rolle für das gehäufte Auftreten einer Struma bei Akromegalie zu diskutieren ist.1. The response of the serum TSH levels after i.v. administration of 500 µg TRF have been determined in normal controls (n=8) and in 37 patients with pituitary tumour or hypothalamic disease. 2. Following hypophysectomy in patients with intrasellar tumours (n=12), the increment in TSH levels after TRF was absent or diminished. 3. Secondary hypothyroidism was found pre-operatively in 3 of 9 patients with intrasellar pituitary adenoma. In these 3 patients, however, a normal TSH response to TRF was found. This result diminishes the diagnostic value of the TRF test regarding the distinction of pituitary and hypothalamic secondary hypothyroidism. A normal TSH response was found, as expected, in the 6 euthyroid patients of this group. 4. The TSH response was found to be normal or elevated in all but one of 7 patients with secondary hypothyroidism due to suprasellar tumour or hypothalamic disease. Primary hypothyroidism is also characterized by an increased TSH response and has to be excluded. 5. Among the patients with active (n=7) or treated (n=6) acromegaly, increased TSH response was found twice, i.e. in one patient of each of the two groups. In both patients, primary hypothyroidism could be excluded. The relevance of this increased TSH response for goitrogenesis in acromegaly is discussed

The control of reproductive physiology and behavior by gonadotropin-inhibitory hormone

Gonadotropin-releasing hormone (GnRH) controls the reproductive physiology and behavior of vertebrates by stimulating synthesis and release of gonadotropin from the pituitary gland. In 2000, another hypothalamic neuropeptide, gonadotropin-inhibitory hormone (GnIH), was discovered in quail and found to be an inhibiting factor for gonadotropin release. GnIH homologs are present in the brains of vertebrates, including birds, mammals, amphibians, and fish. These peptides, categorized as RF amide-related peptides (RFRPs), possess a characteristic LPXRF-amide (X = L or Q) motif at their C-termini. GnIH/RFRP precursor mRNA encodes a polypeptide that is possibly cleaved into three mature peptides in birds and two in mammals. The names of these peptides are GnIH, GnIH-related peptide-1 (GnIH-RP-1) and GnIH-RP-2 in birds, and RFRP-1 and RFRP-3 in mammals. GnIH/RFRP is synthesized in neurons of the paraventricular nucleus of the hypothalamus in birds and the dorsomedial hypothalamic area in mammals. GnIH neurons project to the median eminence, thus providing a functional neuroanatomical infrastructure to regulate anterior pituitary function. In quail, GnIH inhibits gonadal activity by decreasing synthesis and release of gonadotropin. The widespread distribution of GnIH/RFRP immunoreactive fibers in all animals tested suggests various actions within the brain. In accordance, GnIH/RFRP receptor mRNA is also expressed widely in the brain and the pituitary. GnIH/RFRP immunoreactive axon terminals are in probable contact with GnRH neurons in birds and mammals, and we recently demonstrated expression of GnIH receptor mRNA in GnRH-I and GnRH-II neurons in European starlings. Thus, GnIH/RFRP may also inhibit gonadotropin synthesis and release by inhibiting GnRH neurons in addition to having direct actions on the pituitary gland. Intracerebroventricular administration of GnIH/RFRP further inhibits reproductive behaviors in songbirds and rodents, possibly via direct actions on the GnRH system. The expression of GnIH/RFRP is regulated by melatonin which is an internal indicator of day length in vertebrates. Stress stimuli also regulate the expression of GnIH/RFRP in songbirds and rodents. Accordingly, GnIH/RFRP may serve as a transducer of environmental information and social interactions into endogenous physiology and behavior of the animal. Recently, it was shown that GnIH/RFRP and its receptor are also expressed in the gonads of birds, rodents and primates. In sum, the existing data suggest that GnIH/RFRP is an important mediator of reproductive function acting at the level of the brain, pituitary, and the gonad in birds and mammals

Cell Wall Trapping of Autocrine Peptides for Human G-Protein-Coupled Receptors on the Yeast Cell Surface

G-protein-coupled receptors (GPCRs) regulate a wide variety of physiological processes and are important pharmaceutical targets for drug discovery. Here, we describe a unique concept based on yeast cell-surface display technology to selectively track eligible peptides with agonistic activity for human GPCRs (Cell Wall Trapping of Autocrine Peptides (CWTrAP) strategy). In our strategy, individual recombinant yeast cells are able to report autocrine-positive activity for human GPCRs by expressing a candidate peptide fused to an anchoring motif. Following expression and activation, yeast cells trap autocrine peptides onto their cell walls. Because captured peptides are incapable of diffusion, they have no impact on surrounding yeast cells that express the target human GPCR and non-signaling peptides. Therefore, individual yeast cells can assemble the autonomous signaling complex and allow single-cell screening of a yeast population. Our strategy may be applied to identify eligible peptides with agonistic activity for target human GPCRs