Individualized high-dose cabergoline treatment can normalize hyperprolactinemia and hypogonadism in nearly all prolactinomas irrespective of tumor size or preceding treatments. Hyperprolactinemia could be controlled in poor responders within 1 yr with doses higher than 3 mg/wk.

Protein isoforms with or without a single amino acid residue make a subtle difference. It has been documented on a few genes that alternative splicing generated such isoforms; however, the fact has attracted little attention. We became aware of a subtle sequence difference in DRPLA, a polyglutamine disease gene for dentatorubral pallidoluysian atrophy. Some reported cDNA sequences lacked 3 nucleotides (nt) (CAG), which were positioned apart from the expandable and polymorphic CAG repeats and also coded for glutamine. We experimentally confirmed that the difference was indeed generated by alternative splicing utilizing two acceptors separated by 3 nt. In DRPLA, the expression ratio of two mRNA isoforms was almost constant among tissues, with the CAG-included form being major. The glutamine-included protein isoform was more predominantly localized in the nucleus. Database searching revealed that alternative splice acceptors, as well as donors, are frequently situated very close to each other. We experimentally confirmed two mRNA isoforms of 3 nt difference in more than 200 cases by RT-PCR and found interesting features associated with this phenomena. Inclusion of 3 nt tends to result in single amino acid inclusion despite the phase of translational frame. The expression ratio sometimes varied extensively among tissues.

An antiserum raised against human pancreatic growth hormone-releasing factor-(1-40) (hpGRF-40) was found to recognize the rat hypothalamic growth hormone-releasing factor (rhGRF): This antiserum, when given iv to adult male rats, completely abolished GH release induced by a synthetic rhGRF (0.2, 1 microgram/kg BW), and inhibited the physiological GH secretion over 2 days. After passive immunization with anti-hpGRF-40 serum, iv injection of either FK 33-824 (100 micrograms/kg BW), an enkephalin analogue, or clonidine (125 micrograms/kg BW), an alpha-adrenergic agent, failed to stimulate GH release in the unanesthetized rat. These results indicate that the GH-releasing actions of opiatergic and alpha-adrenergic mechanisms are mediated through stimulation of endogenous rhGRF release in the rat.

Secretion of GH occurs in episodic bursts under the dual control of two hypothalamic peptides, GH-releasing factor (GRF) and GH-inhibiting factor (somatostatin, SRIF). Recent studies in rats suggest that episodic GH secretion is generated by the periodic release of GRF, which is associated with the simultaneous withdrawal of SRIF secretion. To test the possibility that GRF discharge is functionally coupled with the withdrawal of SRIF, we investigated whether acute withdrawal of SRIF can induce GRF release by the rat hypothalamus using highly specific antisera against SRIF and rat GRF. In conscious unrestrained rats, i.v. administration of SRIF antiserum at the period of the GH trough induced a rapid onset of the GH secretory surge with a peak value of 309 +/- 67 micrograms/l (mean +/- S.E.M.) 30 min after injection. Pretreatment with antiserum to rat GRF resulted in a approximately 83% suppression of the GH surge induced by SRIF antiserum without affecting the trough GH values. GRF antiserum also significantly inhibited the spontaneous GH surge. In urethane-anaesthetized rats, as in conscious rats, an acute phasic GH release was caused by SRIF antiserum despite the interference of anaesthesia with spontaneous GH secretion. A further surge-like GH secretion was not restored during the next several hours, however, with the GH secretory profile being characterized by a tonic increase in the baseline levels of GH. In the anaesthetized rat antiserum to rat GRF, having no effect on basal GH levels, similarly inhibited by approximately 66% the acute GH surge induced by SRIF antiserum and decreased by about 30% the later sustained rise in GH.(ABSTRACT TRUNCATED AT 250 WORDS)

The capacity of several potent pharmacological agents to increase growth hormone (GH) release was tested in young (3- to 4-month-old) and old (18- to 20-month-old) male Sprague-Dawley rats. Young and old animals were injected with α-methyl-p-tyrosine (250 mg/kg), a catecholamine synthesis inhibitor, followed 60 min later by the α-adrenergic receptor agonist, clonidine hydrochloride (150 μg/kg). Plasma GH levels increased to greater than 276 ng/ml by 30 and 50 min in young rats, whereas values never exceeded 130 ng/ml (p < 0.01) in old rats. Piribedil methane sulfonate (1 mg/ kg), a dopamine receptor agonist, significantly increased GH in young animals 60 min after injection (p < 0.05), but had no effect in old rats. Morphine sulfate (5 mg/kg) increased plasma GH concentrations in young rats to greater than 400 ng/ml at 30, 50 and 70 min after injection, whereas values in old animals never exceeded 300 ng/ml (p < 0.01). 15 min after injection of somatostatin antiserum No. 774 (5 ml/kg), plasma GH levels increased to greater than 750 ng/ml in both young and old rats. Administration of greater volumes of somatostatin antiserum (8 ml/kg) increased GH levels more in old than in young animals 30 and 45 min after injection (p < 0.01). These results indicate that old male rats have less capacity to increase GH in response to agents that normally enhance GH release. This may be the result of a diminished number or affinity of post-synaptic neurotransmitter receptors, or to an increased release of somatostatin. Since somatostatin antiserum increased GH equally or to a greater extent in old than in young animals, aging rats may release more somatostatin or the pituitary may be more sensitive to the inhibitory effects of this hormone.