Jan W. Guzek

Melatonin, pinealectomy, and release of neurohypophysial hormones : in vitro studies

Abstract: The effect of melatonin as well as pinealectomy on the basal and K+‐evoked release of vasopressin and oxytocin from the neurointermediate lobes in vitro was determined. Pineal removal resulted in a diminution of vasopressin and oxytocin release from the neurointermediate lobes in vitro. Melatonin (10−3 or 10−6 M/1) increased vasopressin and oxytocin release from neurointermediate lobes of sham‐operated rats. Nevertheless, when pinealectomized rats served as donors of the neurointermediate lobes, melatonin (10−3 or 10−6 M/1) increased vasopressin release under basal conditions. For the same tissue, melatonin did not affect the oxytocin release either under basal conditions or during depolarization due to excess potassium. When 10−7 M/l melatonin was used, no changes in either vasopressin or oxytocin release were observed in vitro.

The Influence of Melatonin on the Content of Vasopressin and Oxytocin in the Hypothalamus and Neurohypophysis in Euhydrated and Dehydrated Male Rats

Melatonin injected in a single intraperitoneal dose of 100 μg/100 g b. w. to euhydrated rats resulted in a decrease of neurohypophysial oxytocin content but the hypothalamic oxytocin storage as well as the hypothalamo‐neurohypophysial storage of vasopressin were not changed. Following 8 d of once‐daily melatonin treatment the hypothalamic and neurohypophysial oxytocin and vasopressin content was decreased. It might be therefore suggested that melatonin increases the release of neurohypophysial hormones and/or decreases their synthesis.

Luteinizing hormone-releasing hormone and function of the magnocellular vasopressinergic system

Mechanisms by which luteinizing hormone-releasing hormone (LHRH) affects vasopressin secretion were investigated using the isolated rat hypothalamo-neurohypophysial explants. LHRH in a concentration of 4 x 10(-7)M inhibited both the basal and K(+)-stimulated vasopressin release from explants isolated from euhydrated rats. When, however, the tissue was obtained from animals previously salt-loaded, the inhibitory effect of LHRH was completely abolished, thus implying a decrease in the sensitivity to LHRH. LHRH did not affect vasopressin secretion under conditions of generalized blockade of synaptic inputs by 15 mM MgSO(4), suggesting the indirect action of this neurohormone on the hypothalamic magnocellular system. It is concluded that LHRH may play the role of a neuromodulator of vasopressinergic neurones in the rat.

Hypothalamic and neurohypophysial vasopressin and oxytocin in melatonin-treated pinealectomized male rats.

The effect of melatonin on hypothalamic and neurohypophysial vasopressin and oxytocin was investigated in normal and pinealectomized rats. Pinealectomy was followed by a decrease of both vasopressin and oxytocin content in the hypothalamus and neurohypophysis. In unpinealectomized rats, melatonin decreased vasopressin and oxytocin storage in the hypothalamo‐neurohypophysial system. Following pineal removal, melatonin did not augment the pinealectomy‐induced decrease of vasopressin and oxytocin in the neurohypophysis; the hypothalamic storage of both neurohormones was even higher when compared with vehicle‐treated animals.

Luteinizing hormone-releasing hormone and oxytocin response to hyperosmotic stimulation: in vitro study.

It was shown previously that luteinizing hormone-releasing hormone (LHRH) affects the neurohypophysial oxytocin release in water-deprived rats. However, the detailed mechanisms by which LHRH modifies the oxytocin response to hyperosmotic stimulation have not been explained so far. Using the isolated hypothalamo-neurohypophysial explants obtained from euhydrated rats, the effect of LHRH on the oxytocin secretion was studied under conditions of direct osmotic (i.e., Na(+)- evoked) as well as nonosmotic (i.e., K(+)-evoked) stimulation. Additionally, the oxytocin response to LHRH was investigated using the explants obtained from animals drinking 2% saline for eight days (systemic, i. e., both direct and indirect, osmotic stimulation). LHRH significantly enhanced Na(+)- and K(+)-evoked oxytocin release from explants taken from rats drinking tap water, indicating that LHRH could affect the Na(+)/K(+)-dependent depolarization of perikarya of oxytocin neurones. In contrast, LHRH significantly diminished the K(+)-stimulated hormone release when the neurohypophysial complex was obtained from previously salt-loaded rats, suggesting that peripheral osmotic stimulation somehow modifies the sensitivity of oxytocinergic neurones to LHRH (possible mechanisms are discussed). It is concluded that LHRH may participate in the regulation of oxytocin secretion via both direct and indirect impact on magnocellular oxytocinergic neurones depending on the current functional status of the hypothalamo-neurohypophysial complex.

Neurohypophysial response to haemorrhage or dehydration: interactions of vasopressin and luliberin

Abstract Rats, euhydrated, dehydrated for two days or haemorrhaged, were given intracerebroventricularly (i.c.v.) luteinizing hormone releasing hormone (LH-RH) in a daily dose of 100 ng dissolved in 10 μl of 0.9% sodium chloride. In euhydrated rats, a single dose of LH-RH as well as the daily i.c.v. treatment with LH-RH over two days did not significantly affect either the plasma vasopressin concentrations or hypothalamo-neurohypophysial vasopressin content. On haemorrhage (1 ml per 100 g), the increase in plasma vasopressin was almost inhibited and the depletion of neurohypophysial hormone content significantly diminished in animals previously treated with LH-RH. Similarly, LH-RH attenuated markedly the enhanced vasopressin release from the hypothalamo-neurohypophysial system brought about by two-day dehydration. We suggest that LH-RH may have a regulatory role in the hypothalamo-neurohypophysial system especially under conditions of haemorrhage or hyperosmotic dehydration.

The hypothalamic and neurohypophysial oxytocin content as influenced by desmethylimipramine in normal and pinealectomized white male rats

Pinealectomized, sham-operated and non operated control rats were injected intracerebroventricularly (i.c.v.) with a single dose of desmethylimipramine hydrochloride (DMI; 20μg, dissolved in 10μl of normal saline); after 4 hours they were decapitated and the hypothalamic and neurohypophysial oxytocin content was bioassayed using the milk-ejection effectin vitro. DMI decreased oxytocin content of the hypothalamus and neurointermediate lobe in non operated and sham-operated animals. In pinealectomized rats the oxytocin content of the hypothalamus and neurointermediate lobe diminished and could be further reduced by an i.c.v. DMI injection. As shown in animals pretreated with phenoxybenzamine, these events might be only partially related to an increase of alpha-adrenergic transmission.

Endothelin-1 and the release of neurohypophysial hormones under dehydration or haemorrhage

Abstract Rats, euhydrated or dehydrated for 2 days, were given intracerebroventricularly (i.c.v.) endothelin-l (ET-1), once daily in a dose of 10 ng. In euhydrated rats treatment with ET-1 was followed by a decrease in the content of vasopressin (VP) and oxytocin (OT) in the neurointermediate lobe (NL); simultaneously, the plasma concentrations of VP and OT increased. In animals deprived of water for 48 h, plasma concentrations of both VP and OT were increased whereas their content in the NL decreased; if ET-1 was administered during dehydration, however, these effects were markedly attenuated. Under urethane anaesthesia, neither the plasma concentration nor the NL content of both VP and OT were affected by i.c.v. injection of 10 ng ET-1. On haemorrhage (1 ml per 100 g body weight) the plasma levels of both VP and OT were increased. The OT content in the NL was then decreased but no changes in the VP content in the NL were seen on haemorrhage. In haemorrhaged rats prior treatment with ET-1 decreased the VP content in the NL and increased the VP concentration in the plasma when compared with rats haemorrhaged but not treated with ET-1. Simultaneously, the decrease in the neurohypophysial OT content as brought about by bleeding was inhibited and the plasma OT level was distinctly diminished when compared with animals haemorrhaged but not injected with ET-1. These results suggest that ET-1 may have a regulatory role in neurohypophysial function, the regulatory events being possibly modified by afferentation of osmoreceptor origin and also by changes of the central input from arterial pressoreceptors as well as from atrial stretch receptors.

The effects of prostaglandin synthetase inhibitor indomethacin on the hypothalamic and neurohypophysial oxytocin content in euhydrated and dehydrated male white rats.

Rats euhydrated or dehydrated up to eight days were given intraperitoneally indomethacin (IM) twice daily in a dose of 0.2 mg/100 g of initial body weight. A single dose of IM injected to euhydrated animals did not affect the neurohypophysial oxytocic activity but decreased that potency in the hypothalamus. When IM was administered repeatedly during four or eight days, the hypothalamic oxytocic activity did not differ from the respective controls; under such conditions the oxytocic activity in the neurohypophysis increased progressively. Under conditions of dehydration the known depletion of hypothalamic and neurohypophysial oxytocin storage was not affected by indomethacin. It is therefore suggested that impulses of osmoreceptor origin are of distinct importance in determining the function of oxytocinergic neurones under conditions of inhibited prostaglandin synthesis.

Breaking the way: early years of the International Society for Pathophysiology Commission on Teaching

Abstract The establishment of the International Society for Pathophysiology (ISP) Commission on Teaching as well as its organization and activities during the years 1991–1998 are described.