High-dose growth hormone treatment of short children born small for gestational age.

The effect of GH administration was evaluated over 2 yr in 50 short, prepubertal, non-GH deficient children born small for gestational age, who had been randomly allocated to a group receiving no treatment or daily sc GH treatment at a dose of 0.2 or 0.3 IU/kg. At the start of the study, mean age was 5.2 yr, bone age was 4.0 yr, height SDS was -3.5, height velocity SDS was -0.8, weight SDS was -2.7, and body mass index SDS was -1.9. Catch-up growth was observed in none of the untreated and all of the treated children. The response to GH treatment included a near doubling of growth velocity and of weight gain and a mean height increment of more than 2 SDS. GH treatment was associated with a distinct acceleration of bone maturation. The differences between the growth responses evoked by the two GH doses were minor. The prepubertal GH-induced catch-up growth was associated with elevated serum concentrations of insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and osteocalcin, whereas insulin-like growth factor-II levels remained unaltered. GH treatment was well tolerated. In conclusion, high-dose GH administration over 2 yr is emerging as a potential therapy to increase the short stature that results from insufficient catch-up growth in young children born small for gestational age. The long-term impact of this approach remains to be delineated.

Action of dopamine receptor agonists in forebrain and hypothalamus: rotational behavior, ovulation, and dopamine turnover.

An ergolene derivative having a piperazine-phenyl side chain instead of a peptide side chain causes rotational behavior in experimental rats and appears to activate mainly limbic DA receptors when given in vivo, in contrast to amino acid ergot alkaloids, which appear to activate all DA receptors when given systemically. Theophyllamine and caffeine were found to cause considerable enhancement of the action of DA formed from DOPAP AND DA receptor agonists such as apomorphine, piribedil, and amino acid alkaloids on supersensitive DA receptors. Many DA receptor agonists such as apomorphine, piribedil, and CB 154 have in common the property to induce hypothermia in mice, an effect that may be related to actions on limbic DA receptors. Many DA receptors agonists such as apomorphine, piribedil, ergocornine, and CB 154 are able to block ovulation in immature rats treated with PMS. It is likely that this blockade is related to activation of a DA receptor in the median eminence controlling LRF secretion. DA receptor agonists antagonize sexual activity in the female rat, whereas DA receptor blocking agents enhance it. DA neurons may therefore subserve an inhibitory role in the control by hormones of sexual behavior. It is of considerable interest that there appear to exist inhibitory DA receptors with regard to both LRF secretion and sexual behavior.