Effects of postnatal progesterone treatment on ovarian function in adult rats

Summary Long-lasting postnatal progesterone administration in female rats induced an early or delayed ovulatory failure with persistent vaginal estrus. Short-term treatment was ineffective. The beginning and incidence of ovulatory failure appeared to depend on the beginning and duration of progesterone treatment. The necessary duration of progesterone administration exceeds the critical postnatal steroid sensitive period of sexual differentiation of the hypothalamus. Moreover, long-lasting progesterone treatment results in ovulatory failure even if started after termination of this period.     

Unchanged r-RNA-gene dose in mice liver cells of different developmental stages.

The content of ribosomal DNA in mice liver at the beginning as well as near the end of the hematopoietic period was measured by RNA/DAN-hybridization in solution. At both stages the amount of ribosomal DNA was the same and comparable to that of postnatal liver.     

Long-term incubation with mifepristone (MLTI) increases the spine density in developing Purkinje cells: new insights into progesterone receptor mechanisms

Cerebellar Purkinje cells (PC) physiologically reveal an age-dependent expression of progesterone with high endogenous concentrations during the neonatal period. Even if progesterone has been previously shown to induce spinogenesis, dendritogenesis and synaptogenesis in immature PC, data about the effects of progesterone on mature PC are missing, even though they could be of significant therapeutic interest. The current study demonstrates for the first time a progesterone effect, depending on the developmental age of PC. Comparable with the physiological course of the progesterone concentration, experimental treatment with progesterone for 24 h achieves the highest effects on the dendritic tree during the early neonate, inducing an highly significant increase in dendritic length, spine number and spine area, while spine density in mature PC could not be further stimulated by progesterone incubation. Observed progesterone effects are certainly mediated by classical progesterone receptors, as spine area and number were comparable to controls when progesterone incubation was combined with mifepristone (incubation for 24 h), an antagonist of progesterone receptors A and B (PR-A/PR-B). In contrast, an increase in the spine number and area of both immature and mature PC was detected when slice cultures were incubated with mifepristone for more than 72 h (mifepristone long-time incubation, MLTI). By including time-lapse microscopy, electron microscopic techniques, PCR, western blot, and MALDI IMS receptor analysis, as well as specific antagonists like trilostane and AG 205, we were able to detect the underlying mechanism of this diverging mifepristone effect. Thus, our results provide new insights into the function and signaling mechanisms of the recently described progesterone receptor membrane component 1 (PGRMC1) in PC. It is highly suitable that progesterone does not just induce effects by the well-known genomic mechanisms of the classical progesterone receptors but also acts through PGRMC1 mediated non-genomic mechanisms. Thus, our results provide first proofs for a previously discussed progesterone-dependent induction of neurosteroidogenesis in PC by interaction with PGRMC1. But while genomic progesterone effects mediated through classical PR-A and PR-B seem to be restricted to the neonatal period of PC, PGRMC1 also transmits signals by non-genomic mechanisms like regulation of the neurosteroidogenesis in mature PC. Thus, PGRMC1 might be an interesting target for future clinical studies and therapeutic interventions.     

Response to an antiestrogen as a criterion for hormonal sensitivity of endometrial cancer]

A test is described for the evaluation of hormone sensitivity of endometrial cancer in vivo. The concentrations of progesterone and estradiol receptors, and the activities of ornithine-decarboxylase and 17 beta-hydroxysteroid oxido-reductase enzymes have been measured in the tumor, before and after administration of the anti-estrogen tamoxifen. The responses observed, in particular the increase of progesterone receptor, could allow a more rational approach to hormonal therapy of endometrial cancer.     

Pineal melatonin rhythms and the timing of puberty in mammals

Summary The direction of change in daylength provides the seasonal time cue for the timing of puberty in many mammalian species. The pattern of melatonin secretion from the pineal gland transduces the environmental light-dark cycle into a signal influencing the neuroendocrine control of sexual maturation. The change in duration of nocturnal melatonin secretion is probably the key feature of the melatonin signal which conveys daylength information. This information may also be used by neuroendocrine axes controlling seasonal changes in pelage colour, growth and metabolism. The mechanism of action of melatonin on neuroendocrine pathways is unknow. Although the ability to synthesize and secrete melatonin in a pattern that reflects the duration of the night may not occur until the postnatal period, the rodent and ovine foetus has the ability to respond in utero to photoperiodic cues to which its mother is exposed in late gestation. Transplacental passage of maternal melatonin is likely to be the mechanism by which photoperiodic cues reach the foetus. Species which do not exhibit seasonal patterns of puberty, such as the human, also secrete melatonin in a pattern which reflects the environmental light-dark cycle, but they do not respond reproductively to the seasonal melatonin information.     

Pineal melatonin rhythms and the timing of puberty in mammals

The direction of change in daylength provides the seasonal time cue for the timing of puberty in many mammalian species. The pattern of melatonin secretion from the pineal gland transduces the environmental light-dark cycle into a signal influencing the neuroendocrine control of sexual maturation. The change in duration of nocturnal melatonin secretion is probably the key feature of the melatonin signal which conveys daylength information. This information may also be used by neuroendocrine axes controlling seasonal changes in pelage colour, growth and metabolism. The mechanism of action of melatonin on neuroendocrine pathways is unknown. Although the ability to synthesize and secrete melatonin in a pattern that reflects the duration of the night may not occur until the postnatal period, the rodent and ovine foetus has the ability to respond in utero to photoperiodic cues to which its mother is exposed in late gestation. Transplacental passage of maternal melatonin is likely to be the mechanism by which photoperiodic cues reach the foetus. Species which do not exhibit seasonal patterns of puberty, such as the human, also secrete melatonin in a pattern which reflects the environmental light-dark cycle, but they do not respond reproductively to the seasonal melatonin information.     

Action of various progestational hormones on the electric activity of the rat myometrium in pregnancy after biovariectomy

8-day-pregnant rats were ovariectomized, then injected im with progestagens and estrogens while their uterine motility and electrical activity were being recorded simultaneously with a strain gauge and 2 bipolar electrodes. The injections, known to maintain pregnancy after ovariectomy, were progesterone 50 mg/kg, progesterone with estradiol 5 mcg/kg, or medroxyprogesterone acetate 25 mg/kg. Base line recordings for 20 minutes showed the normal pregnant state of brief periods of synchromous electrical and mechanical activity. After ovariectomy, untreated controls exhibited increased duration of synchronized mechanical and electrical activity and height of contractions. When any of the 3 progestagen treatments coincided with ovariectomy, synchrony was decreased and the intervening interval lasted longer. These procedures demonstrated how quickly the hormonal deficit due to ovariectomy is compensated for when ablation is performed before placental progesterone synthesis has begun.     

Effect of synthetic ACTH (beta 1-23 corticotropin) on gestation and parturition in rats]

Daily administration of synthetic ACTH (betaI-23 corticotrophine) from day 15 of pregnancy induces delay or inhibition of parturition in normal or ovariectomized Rats injected or not with estradiol. Parturition takes place at approximatively normal time, when ACTH is stopped and estradiol continued. Radio-immunological assays show an increase of blood progesterone level after ACTH administration in castrated, but not in castrated and adrenalectomized Rats. Mechanisms of ACTH action are discussed.     

The effects of intraventricular injection of 6-hydroxydopamine on the sleep of kittens during development]

Intraventricular injection of 6-hydroxydopamine does not modify the states of alertness in the Kitten, if it is performed in the first week of postnatal life. At three weeks of age, it induces the same sleep impairments as those observed in the adult Cat. Therefore, in the immediate postnatal period, sleep control is not achieved through the monoaminergic systems.     

Influence of gonadal hormones on the devleoping amphibian brain: Changes in ribonucleic acid,protein and activity levels of acetylcholinesterase on in vivo administration of progesterone

Summary The levels of RNA and protein and activity levels of acetylcholinesterase decreased in the brain of developing tadpoles of 13–15-day-oldBufo melanostictus on in vivo administration of progesterone (200 g/0.1 ml refined peanut oil). These changes suggest decelaration in the activity of the protein-synthetic machinery in progesterone administered animals.Acknowledgment: I am thankful to Dr.A. R. Kasturi Bai, Head of the Department of Zoology, Bangalore University for offering facilities to conduct the study.     

Effects of repeated administration of potassium canrenoate (SC-14266) on serum gonadotrophin,prolactin, testosterone and progesterone in male rats

Summary Chronic administration of potassium canrenoate (SC-14266), a water-soluble anti-aldosterone agent, increased serum LH levels in male rats without altering serum levels of FSH, prolactin, testosterone and progesterone. The increase in serum LH may be due to the anti-androgenic effect of potassium canrenoate.Acknowledgments. The authors thank the Rat Pituitary Hormone Distribution Program, NIAMDD, NIH and Dr A.F. Parlow for radioimmunoassay materials.     

Influence of treatment duration on audiogenic seizure susceptibility during barbiturate withdrawal in rats

Summary Barbiturate withdrawal seizure susceptibility in rats increased with increasing duration of treatment during a 15-day treatment period in which the animals were given an i.p. dose of sodium barbital every 12 h. This method of producing dependence has clear advantages over previously described methods.     

Differential displacement of cells from the median eminence into the arcuate nucleus during puberty. Effects of melatonin administration

A displacement of catecholaminergic-positive and catalase-containing cells from the median eminence into the arcuate nucleus at puberty has been described previously. This study reports on the displacement phenomena after postnatal administration of melatonin. Catalase-positive cells undergo a delayed displacement from the median eminence into the arcuate nucleus. However, part of this cell population lags behind within the median eminence. This differential reaction of cell displacement by catalase-positive cells is considered as a special reaction of these cells to melatonin administration.     

Influence of treatment duration on audiogenic seizure susceptibility during barbiturate withdrawal in rats

Barbiturate withdrawal seizure susceptibility in rats increased with increasing duration of treatment during a 15-day treatment period in which the animals were given an i.p. dose of sodium barbital every 12 h. This method of producing dependence has clear advantages over previously described methods.     

Neuronal degeneration in the striatum of the groggy rat: a new mutant with a movement disorder.

A new mutation displaying abnormal movement was obtained in the progeny of a female Wistar rat which had been given 10 mg/kg methylnitrosourea at an early stage of the gestational period. Genetic studies revealed that the character is inherited by an autosomal single recessive gene, and we designated this mutation groggy (gene symbol gr). The abnormal movement of the groggy rat was first apparent around postnatal day 15, while the histological studies revealed the appearance of numerous necrotic neurons in the striatum of the groggy rat on postnatal days 60 and 120.     

Differential displacement of cells from the median eminence into the arcuate nucleus during puberty. Effects of melatonin administration

Summary A displacement of catecholaminergic-positive and catalase-containing cells from the median eminence into the arcuate nucleus at puberty has been described previously. This study reports on the displacement phenomena after postnatal administration of melatonin. Catalase-positive cells undergo a delayed displacement from the median eminence into the arcuate nucleus. However, part of this cell population lags behind within the median eminence. This differential reaction of cell displacement by catalase-positive cells is considered as a special reaction of these cells to melatonin administration.     

Attempt to induce, in the rat, a hepatitis of cirrhotic origin, using amino steroids: holaphyllaminol or amino 3-beta hydroxy-20-beta pregnene-5]

Holaphyllaminol, or Amino-3 beta-Hydroxy-20-beta Pregnene-5, was administered by gastric tube to male Wistar rats at dose of 50, 100 and 200 mg/kg/24 hr respectively, during 10, 20, 40 and 80 days. This substance provokes hepatic lesions beginning at the periportal region, the characteristics of which are a cholestasis, a canalar proliferation and a fibrosis. The interest of these alterations lies in the fact that they present the same features as certain human chronic hepatitis; their progression, a function of the dose of the toxin and the duration of treatment, may make possible to realisation of a model of experimental chronic hepatitis.     

Effect of photoperiod on early changes in the neonatal rat pineal gland

Summary It is concluded that photoperiod has little direct effect on the mitotic activity or morphological development of the pineal parenchymal cell of the rat in the early postnatal period.     

Bioavailability of progesterone enhanced by intranasal spraying

Summary The bioavailability of progesterone (P) in terms of area under time-concentration curve and maximal concentration in the serum and cerebrospinal fluid was studied in adult ovariectomized rhesus monkeys following the administration of P as a nasal spray, i.v. or i.m. injections, nasal or eye drops. The bioavailability of P in both the body fluids was found to be considerably higher following its being sprayed intranasally.This work was supported by the World Health Organization, Geneva.