Multihormonal Control of Pre-Pro-Somatostatin mRNA Levels in the Periventricular Nucleus of the Male and Female Rat Hypothalamus

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Abstract
The influence of sex steroids as well as the possible involvement of dopaminergic pathways in the modulation of pre-pro-somatostatin (SS) mRNA levels was investigated by quantitative in situ hybridization in the hypothalamic periventricular nucleus (PeN) in adult male and female rats. In situ hybridization was performed using a [35S]-labeled cDNA probe encoding pre-proSS mRNA. Gonadectomy performed 14 days earlier decreased the mean number of silver grains/neuron corresponding to the relative pre-proSS mRNA levels by 22% in male and by 18–28% in female rats. A 14-day treatment with the nonaromatizable androgen dihydrotestosterone (DHT) increased the mean number of silver grains/neuron by 34–40%) in gonadectomized animals of both sexes. Moreover, administration of 17β-estradiol (E2, 0.25 µg twice daily) increased pre-proSS mRNA levels by 40% in ovariectomized (OVX) animals. Such treatment with E2 or DHT changed the frequency distribution profile of the hybridization signal intensity, thus increasing the percentage of highly labeled neurons (>61 grains/neuron) by 10 to 12-fold. A 14-day treatment with the D2 dopamine receptor agonist bromocriptine (BRO) increased pre-proSS mRNA levels by 15 and 28% in intact female and OVX animals, respectively, while the dopaminergic antagonist haloperidol (HAL) decreased the value of this parameter by 20 and 30%. Furthermore, BRO increased pre-proSS mRNA levels by 10 and 20% in intact and castrated male rats, respectively, whereas HAL decreased pre-proSS mRNA levels by 25 and 14% in the same groups of animals. Administration of E2 in combination with HAL in OVX animals increased pre-proSS mRNA levels by 70% compared to those measured in OVX animals treated with HAL alone. In HAL-treated castrated male rats, administration of DHT increased the relative pre-proSS mRNA levels by 35% compared to those measured in castrated animals treated with HAL alone. The present data clearly demonstrate that androgens and estrogens as well as dopamine-mediated mechanisms could play a regulatory role in pre-proSS mRNA levels in somatostatinergic neurons in the hypothalamic PeN in both male and female rats.