Impaired estrogen-induced negative feedback on gonadotropin secretion in patients with gonadotropin-secreting and nonfunctioning pituitary adenomas.

BACKGROUND: Several in vitro studies suggest that gonadotropin-secreting pituitary adenomas (Gn-omas) and non functioning pituitary adenomas (NFPA) originate from gonadotroph cells. Patients with Gn-oma and NFPA frequently show abnormal gonadotropin response to TRH. The aim of the study was to investigate whether the estrogen-induced negative feedback is operating in either patients with Gn-oma or NFPA. MATERIALS AND METHODS: Serum gonadotropin levels were evaluated at 24 h after ethinylestradiol administration (1 mg per os; EE2 test) in seven patients with a diagnosis of Gn-oma, based on the presence of high follicle-stimulating hormone (FSH) and/or lutenising hormone (LH) levels with normal or high levels of sex steroids, in 22 patients with NFPA with normal or low levels of gonadotropin and sex steroids, and 30 sex- and age-matched healthy subjects. A normal response to EE2 test was arbitrarily defined as a serum LH and FSH decrease of at least 40 and 30% below basal levels. RESULTS: Among patients with Gn-oma, only one had a normal FSH inhibition and another, a normal LH inhibition. Among the 22 patients with NFPA, the EE2 test caused a normal FSH or LH reduction in 10 and 15, respectively, while a normal reduction of both FSH and LH was observed in nine. CONCLUSIONS: The study demonstrates that estrogen-induced negative feedback of gonadotropin secretion is disrupted in almost all patients with Gn-oma and in half of those with NFPA. This defective feedback is reminiscent of the resistance to thyroid hormones and glucocorticoids observed in patients with thyroid-stimulating hormone- (TSH-) and adrenocorticotropic hormone- (ACTH-)secreting adenomas, respectively.

Stimulated secretion of pituitary hormones in normal humans: a novel direct assessment from blood concentrations.

Gland responsiveness is usually assessed by administering suitable secretagogues and measuring the resulting hormone concentration in blood after the specific stimulus. Such response-to-stimulus tests are routinely conducted for the clinical diagnosis of pathologies involving the pituitary hormones growth hormone, prolactin, luteinizing hormone, follicle stimulating hormone, adrenocorticotropic hormone, and thyrotropin hormone. However, the current evaluation approaches, based on the maximum peak value or the (normalized) area under the curve, are inadequate under several respects. A more physiologically based index of responsiveness is the amount of released hormone. This is not directly accessible but is typically estimated by (computationally expensive) deconvolution analysis. The present work derives a simple formula yielding the amount of released hormone as a linear combination of blood concentrations through proper weights depending on hormone kinetics and sampling protocol. The weights are derived and reported for all six pituitary hormones and the more common sampling protocols. A validation study involving 174 test experiments has been carried out. The use of the formula shows excellent agreement with the cumulative secretion estimates obtained through deconvolution analysis.

Assessment of a combined anterior pituitary function test in beagle dogs: rapid sequential intravenous administration of four hypothalamic releasing hormones.

A combined anterior pituitary (CAP) function test was assessed in eight healthy male beagle dogs. The CAP test consisted of sequential 30-second intravenous administrations of four hypothalamic releasing hormones in the following order and doses: 1 microgram of corticotropin-releasing hormone (CRH)/kg, 1 microgram of growth hormone-releasing hormone (GHRH)/kg, 10 micrograms of gonadotropin-releasing hormone (GnRH)/kg, and 10 micrograms of thyrotropin-releasing hormone (TRH)/kg. Plasma samples were assayed for adrenocorticotropin, cortisol, GH, luteinizing hormone (LH), and prolactin (PRL) at multiple times for 120 min after injection. Each releasing hormone was also administered separately in the same dose to the same eight dogs in order to investigate any interactions between the releasing hormones in the combined function test. Compared with separate administration, the combined administration of these four hypothalamic releasing hormones caused no apparent inhibition or synergism with respect to the responses to CRH, GHRH, and TRH. The combined administration of these four hypothalamic releasing hormones caused a 50% attenuation in LH response compared with the LH response to single GnRH administration. The side effects of the combined test were confined to restlessness and nausea in three dogs, which disappeared within minutes after the administration of the releasing hormones. It is concluded that with the rapid sequential administration of four hypothalamic releasing hormones (CRH, GHRH, GnRH, and TRH), the adenohypophyseal responses are similar to those occurring with the single administration of these secretagogues, with the exception of the LH response, which is lower in the CAP test than after single GnRH administration.

Valoración aminérgica en pacientes con tumor hipofisiario productor de prolactina / Valoration aminergic in patients with hypophyseal prolactin producing tumors

Se estudia la importancia de las teorías etiológicas actuales de los tumores productores de prolactina (PRL). Así, los tumores productores de PRL pueden considerarse como un síndrome de múltiples etiologías, en las que participan diferentes estímulos peptidérgicos hipotalámicos. En pacientes con diagnóstico de tumor productor de PRL se estudiaron: A) la regulación dopaminérgica que estimula o inhibe la secreción de PRL, B) la neurotransmisión gabaminérgica que tambien estimula la secreción de PRL en el sistema nervioso central y lactotropo hipofisiario; y C) la vía serotoninérgica que produce liberación de PRL. Estos tipos de estímulos pueden ser la causa subyacente de la hiperplasia celular que origina la secreción de PRL .

Canine and feline thyroid function assessment with the thyrotropin-releasing hormone response test.

A canine and feline pituitary-thyroid function test based on thyrotropin-releasing hormone (TRH) stimulation of endogenous thyrotropin is described. Serum thyroxine is measured before and after stimulation with TRH. A positive response to TRH indicated a functionally intact pituitary-thyroid axis. At TRH doses of 0.002 to 10.0 mg/kg of body weight, dose response of serum thyroxine to TRH stimulation was determined. Increasing the dose of TRH increased the duration, but not the magnitude, of thyroxine stimulation. At TRH doses greater than 0.1 mg/kg, drug side effects were salivation, defecation, urination, vomition, miosis, tachycardia, and tachypnea. A useful procedure for pituitary-thyroid function testing was serum thyroxine measurement before and 6 hours after TRH (0.1 mg/kg) stimulation.

Actions of thyrotropin-releasing hormone on gastrointestinal functions in man. III. Inhibition of gastric motility in response to distension.

The intragastric pressure/volume relationship has been measured in six healthy volunteers. Increased gastric motility was achieved by gastric distension, by stepwise increasing the volume from 0--600 ml. When thyrotropin-releasing hormone (TRH), 0.04 mg/h, was infused concomitantly in the individuals, gastric motility was significantly inhibited (p less than 0.05) and, with 1 mh/h of TRH, nearly abolished compared with the saline control test. The basal pressure was unaffected at 0.04 mg/h, whereas a significant rise was seen after 1 mg/h of TRH (p less than 0.05) compared with the control test. In three of the subjects the effect of rapid injection of TRH (0.2 mg), followed by infusion of TRH (0.6 mg/h), on the stimulated gastric motility was analysed. After the injection of TRH, almost no motor activity was observed during the 15-min observation period. It is concluded that TRH has a potent inhibiting effect on gastric motility, and the possible physiological role of TRH in the gastric regulation in man is discussed.

Assessment of anterior pituitary function during the post-partum period.

In order to assess anterior pituitary function during the puerperium, 20 women were studied by 14 intravenous LRH and 10 TRH stimulation tests within 2-10 days post-partum. The basal FSH level (150-340 ng/ml) was within the normal non-pregnant range for the follicular phase of the menstrual cycle (50-350 ng/ml) and did not increase after 100 mug of synthetic LRH. The TSH (3.3-8.8 muU/ml) was high and increased after 200 mug of synthetic TRH about twofold. Obstetrical parameters (e.g. milk excretion, pregnancy complication, type of delivery or the amount of bleeding during delivery) were not associated with significant changes in FSH or TSH levels or in the responses to TRH stimulation.