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Plasma ACTH, beta-endorphin and alpha-melanocyte-stimulating hormone levels were evaluated in the inferior petrosal sinuses and in the periphery of 22 patients affected by Cushing's disease, 11 patients with other pituitary diseases subjected to simultaneous and bilateral inferior petrosal sinus sampling and in the peripheral blood of 15 normal subjects. In patients with Cushing's disease ACTH, beta-endorphin and alpha-melanocyte-stimulating hormone levels in the inferior petrosal sinus ipsilateral to the adenoma were significantly higher than in the periphery and in the contralateral inferior petrosal sinus (p < 0.01, p < 0.01 and p < 0.05, respectively). In patients with other pituitary diseases only ACTH and beta-endorphin, but not alpha-melanocyte-stimulating hormone levels in both inferior petrosal sinuses were significantly higher than in the periphery (p < 0.01). Furthermore, no difference was found in the peripheral blood among patients with Cushing's disease, patients with other pituitary diseases and normal subjects for ACTH and beta-endorphin level. By contrast, in patients with Cushing's disease peripheral alpha-melanocyte-stimulating hormone levels were significantly higher than in patients with other pituitary diseases and in normal subjects (p < 0.05). In conclusion, the results of the present study suggest that only in patients with Cushing's disease, but not in patients with other pituitary diseases, alpha-melanocyte-stimulating hormone is released by adenomatous pituitary corticotrophs together with ACTH and beta-endorphin.

The role of somatostatin (SS) receptor subtype 1 (SSTR1) in mediating the inhibitory effect of SS on growth hormone (GH) secreting pituitary tumors has been recently demonstrated. In the present study, we evaluated the effect of the selective SSTR1 agonist BIM-23745 on in vitro GH secretion in GH-secreting pituitary tumor cells, deriving from patients resistant or partially responsive to octreotide long-acting release (octreotide-LAR) or lanreotide therapy in vivo and expressing SSTR1 mRNA. In addition, the inhibiting effect of BIM-23745 on the GH secretion was compared with that of octreotide. Our data demonstrate that (1) SSTR1 receptor was present in 56.25% (9/16) of the GH-secreting adenomas examined; (2) in all GH-secreting pituitary tumors that expressed SSTR1, BIM-23745 significantly inhibited GH secretion in vitro, and (3) when SSTR1 subtype was present in tumors from patients resistant to octreotide-LAR or lanreotide therapy, BIM-23745 was able to inhibit the in vitro GH secretion. In conclusion, the results of the current study suggest that SS analogs selective for the SSTR1 may represent a further useful approach for the treatment of acromegaly in patients resistant or partially responsive to octreotide-LAR or lanreotide treatment in vivo.

The use of intercavernous sinus phlebography for the diagnosis and neurosurgical treatment of pituitary adenomas has enabled the collection of selective venous samplings of the inferior petrosal sinuses (IPSs), where prolactin (PRL) levels can be measured before the hormone becomes excessively diluted in the systemic circulation. In the present study, plasma PRL levels were studied in the right and/or left IPS and, simultaneously, in the peripheral circulation of: (1) normoprolactinemic patients affected with various pituitary disorders which required phlebographic procedures; (2) hyperprolactinemic patients with negative radiological and computed tomographic (CT) signs of pituitary adenomas and (3) adenomatous hyperprolactinemic patients. In the 17 normoprolactinemic patients, the plasma PRL concentration in the IPSs was significantly higher (3.5 times; p less than 0.01) than in the peripheral circulation. In the 11 hyperprolactinemic patients with negative radiological and CT signs of pituitary adenomas, the central gradient for PRL was significantly higher (2.8 times; p less than 0.05) than in the peripheral circulation. No significant difference was detected between PRL concentrations in the left and right IPSs. In the 11 adenomatous hyperprolactinemic patients, there was a significant (p less than 0.01) central gradient for PRL 3.8 times higher than in the peripheral circulation on the ipsilateral side of the tumor. Furthermore, the plasma PRL concentration in the ipsilateral IPS was significantly higher (3.4 times; p less than 0.05) than that in the contralateral sinus. In conclusion, the present study shows that a clear-cut concentration gradient exists between plasma PRL levels in the IPSs and in the peripheral circulation of normoprolactinemic and hyperprolactinemic patients with negative radiological and CT signs of pituitary adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

The tuberoinfundibular dopaminergic (TIDA) neurons appear to present remarkable differences from the nigrostriatal and mesocortical dopaminergic (DA) systems. The hormonal feedback of prolactin on TID

A comparison of the kinetics of dopamine uptake was made in synaptosomal preparations of the median eminence, striatum and olfactory tubercle. Double reciprocal Lineweaver-Burk plots of the initial velocity versus the concentration of dopamine yielded a single straight line in all three areas. The Michaelis constant (Km) in the median eminence (1.8 +/- 0.9 X 10(-6) M) was significantly higher (p0.05) than in the striatum (4.2 +/- 0.8 X 10(-8) M) or olfactory tubercle (6.3 +/- 1.9 X 10(-8) M). Uptake in the median eminence appeared to be predominantly into dopaminergic terminals since preincubation with desipramine did not affect the maximum velocity (Vmax) of dopamine uptake. Observed uptake was predominantly due to transport across the neuronal membrane and not into storage granules, since reserpine only caused a small decrease in uptake. The low affinity of dopamine uptake in median eminence synaptosomes is consistent with the neurosecretory nature of these terminals, whereas, in the striatum and olfactory tubercle, high affinity reuptake is consistent with the role of dopamine as a neurotransmitter.

The kinetics of dopamine (DA) uptake were studied in synaptosomal preparations of the neurointermediate lobe (NIL) of the pituitary gland, a region containing the terminals of the tuberoinfundibular dopaminergic neurons. Lineweaver-Burk plots of the initial velocity of DA uptake versus the concentration of DA yielded a single straight line in the NIL. The Km values in the NIL of the rat and the steer were 2.2+/-0.5 x 10(-6) M and 2.0+/-0.1 x 10(-6) M, respectively. The uptake was predominantly into dopaminergic terminals since preincubation with desipramine did not affect the Vmax or Km of DA uptake. Observed uptake was predominantly due to transport across the neuronal membrane and not into storage granules, since reserpine caused only a small decrease in uptake. The concentration of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the NIL was 3.6 ng/mg protein. The ratio of DA to DOPAC in the NIL (3.73) was similar to that obtained in the medial basal hypothalamus, another region innervated by the tuberoinfundibular dopaminergic neurons. The kinetics of DA uptake in the nerve terminals of the NIL are similar to those observed in the DA terminals in the median eminence. The affinity of uptake in the terminal fields of the tuberoinfundibular system is considerably lower than in terminals of the mesolimbic and nigrostriatal dopaminergic terminals.