Endocrine Effects of the Mammalian Pineal

The current status of knowledge concerning the mammalian pineal'sendocrine effects and the possible mechanisms for their mediationis reviewed and discussed. The diversity, physiological relations,and variability of the pineal's peripheral effects, and theconstancy, rapidity, and homeostatic nature of its central andbehavioral effects are consistent with the view that the pineal'sprimary action is on brain tissue. It remains probable thaton a seasonal basis, the pineal's vegetative and homeostaticeffects may contribute to the adaptive physiological changesin particular mammalian species under the influence of changesin photoperiod and possibly other environmental factors.     

Isolation of Avian and Mammalian Pineal Indoles and Antigonadotropic Factors

With mild extraction and separation methods it was possibleto locate and isolate, starting with 100 or 200 g of pinealtissue, different indoles, with mass spectra identical to thoseof synthetic melatonin, 5-HIAA and 5-MIAA. It was also possibleto isolate fractions, which showed, in thin-layer chromatographicstudies, spots with R_f values identical to those of synthetic5-HTL and 5-MTL. A "non-melatonin" antigonadotropin, in an in vivo bioassay,was also isolated from sheep pineals and partially purified. Antigonadotropic and gonadotropic activities, which differ fromthe above described indoles, could be located with the samemethods. Some of these compounds acted on the hypothalamus,while others acted on the anterior hypophysis in vitro.     

Viruses in the Mammalian Male Genital Tract and Their Effects on the Reproductive System

This review describes the various viruses identified in the semen and reproductive tracts of mammals (including humans), their distribution in tissues and fluids, their possible cell targets, and the functional consequences of their infectivity on the reproductive and endocrine systems. The consequences of these viral infections on the reproductive tract and semen can be extremely serious in terms of organ integrity, development of pathological and cancerous processes, and transmission of diseases. Furthermore, of essential importance is the fact that viral infection of the testicular cells may result not only in changes in testicular function, a serious risk for the fertility and general health of the individual (such as a fall in testosteronemia leading to cachexia), but also in the possible transmission of virus-induced mutations to subsequent generations. In addition to providing an exhaustive account of the data available in these domains, this review focuses attention on the fact that the interface between endocrinology and virology has so far been poorly explored, particularly when major health, social and economical problems are posed. Our conclusions highlight the research strategies that need to be developed. Progress in all these domains is essential for the development of new treatment strategies to eradicate viruses and to correct the virus-induced dysfunction of the endocrine system.     

The Mammalian Pineal Expresses the Cone but Not the Rod Cyclic GMP Phosphodiesterase

Abstract: To determine the presence of cone or rod cyclic GMP phosphodiesterase (EC 3.1.4.17) in the mammalian pineal, extracts from adult rat and bovine pineals were injected onto a Mono Q anion-exchange HPLC column and eluted with an NaCl linear gradient. Fractions were immunoadsorbed with monoclonal antibodies specific to rod and cone phosphodiesterases (ROS-1) and to calmodulin-phosphodiesterase complexes (ACC). Profiles were assayed with 10 µmol/L [³H]cyclic GMP in the presence of calcium-calmodulin, histone, or trypsin. Rat and bovine pineals displayed a single peak of activity recognized by ROS-1, which corresponded to the activity of the cone but, not to the rod in bovine retina. ROS-1 immunoadsorbed ∼80% of the activity in the 60-day-old rat pineal but only 26% of the activity in bovine pineal. ACC immunoadsorbed the remaining activity in both species. Western blot analysis of rat pineal extracts revealed three polypeptides of ∼87, 15, and 10 kDa when probed with a rod/cone phosphodiesterase-specific antiserum. The specific activity of the cone-like phosphodiesterase in 10-day-old rat pineals was twice that of this isozyme in the bovine retina and 150 times that in the bovine pineal. The specific activity of phosphodiesterase in rat pineals decreased with age. We conclude that an enzyme with biochemical and antigenic characteristics similar to cone, but distinct from rod phosphodiesterase, is present in bovine and rat pineals.     

前列腺素D2及其受体与哺乳动物生殖

前列腺素D2(PGD2)是前列腺素(PGs)家族成员之一,广泛分布于各种哺乳动物组织中,并发挥多种生理功能。PGD,可以促进睡眠、诱导过敏反应、抑制血小板凝集及松弛平滑肌等,并且在生殖系统中起重要作用。机体中存在生化和免疫功能截然不同的两类前列腺素D合成酶(PGDs)：脑型PGDS(L-PGDS)和生血型PGDS(hPGDS)。生殖系统中,L-PGDS主要存在于雄性生殖道,可能在睾丸发育、精子发生、精子成熟以及血一睾和血一附睾屏障等方面发挥重要作用。hPGDS在妊娠时期的子宫内膜和胚胎滋养层中表达,由其产生的PGD2可能通过DP和CRTH2两种受体来维持妊娠。此外,PGD2还可能与女性不孕以及精子在雌性生殖道内的运输等有关。     

Interspecific Variation in the Reproductive Response of Acacia Species to Protection from Large Mammalian Herbivores

We quantified the fruit set of four Acacia spp. inside and outside of long-term experimental exclosures in order to examine the fitness consequences of herbivory by large mammals. We found a considerable interspecific variation in the reproductive fitness costs of herbivory in four African Acacia spp. Acacia nilotica and A. brevispica respond to protection from large mammalian herbivores by greatly increasing their seed set. In contrast, there was little or no increase in seed set in A. mellifera and A. etbaica . The reasons for these differences are not known, but may be related to armament morphologies.     

Physiological Pineal Effects on Female Reproductive Function of Laboratory Rats: Prenatal Development of Pups,Litter Size and Estrous Cycle in Middle Age

The present study investigates whether and how the pineal or its hormone melatonin influences female reproductive functions, namely the litter size, prenatal development of offsprings, and estrous cyclicity, especially its age‐related cessation in a non‐seasonal breeder, the laboratory rat. Wistar rats were maintained under a 24 h light‐dark (12L∶12D) cycle. Female rats were divided into 3 groups: non‐operated (NO), sham‐operated (SX), and pinealectomized (PX). Surgeries were performed in 35–40 day‐old females. Starting at an age between 70 days and 7 months, female rats of all 3 groups were repeatedly mated with intact males. PX mothers more frequently delivered pups with malformations (e.g., taillessness, hydronephrosis, 7 out of 1263 pups) than control rats (0/1323; p<0.007). In the first delivery at 3 months of age, but not at later ages, PX mothers delivered more pups of lower body weight than control animals (p<0.001). Examination of vaginal smears showed that almost all female rats of the NO, SX, and PX groups had 4‐day estrous cyclicity when they were young–between 60 days and 5 months of age. At an age of 17 to 18 months, most female rats of the NO and SX groups showed irregular, continuously diestrous or pseudopregnancy‐like patterns, and 4‐day estrous cyclicity was found in only 10% of the NO or SX animals. In contrast, about 50% of the PX rats showed 4‐day estrous cyclicity at this older age (p< 0.001). Melatonin, when added to drinking water (0.4 mg/L) for 16 days during the dark phase increased the frequency of diestrous phase, except in continuously diestrous rats and very few others. This melatonin effect was strong in PX rats but relatively weak in SX rats. In conclusion, the pineal hormone appears to influence various reproductive functions and developmental processes, especially pregnancy and the timing of reproductive aging in rats. The effects of pinealectomy are more prominent at an age of 60 to 80 days (i.e., shortly after puberty) and at the beginning of the cessation of cycles in middle‐aged females.     

Presynaptic and Postsynaptic Effects of Neuropeptide Y in the Rat Pineal Gland

Abstract: Neuropeptide Y is colocalized with noradrena-line in sympathetic fibers innervating the rat pineal gland. In this article we present a study of the effects and mechanisms of action of neuropeptide Y on the pineal noradrenergic transmission, the main input leading to the rhythmic secretion of melatonin. At the presynaptic level, neuropeptide Y inhibits by 45%, with an EC₅₀ of 50 n M , the potassium-evoked noradrenaline release from pineal nerve endings. This neuropeptide Y inhibition occurs via the activation of pertussis toxin-sensitive G protein-coupled neuropeptide Y-Y2 receptors and is independent from, but additive to, the α₂-adrenergic inhibition of noradrenaline release. At the postsynaptic level, neuropeptide Y decreases by a maximum of 35%, with an EC₅₀ of 5 n M , the β-adrenergic induction of cyclic AMP elevation via the activation of neuropeptide Y-Y1 receptors. This moderate neuropeptide Y-induced inhibition of cyclic AMP accumulation, however, has no effect on the melatonin secretion induced by a β-adrenergic stimulation. On the contrary, in the presence of 1 m M ascorbic acid, neuropeptide Y potentiates (up to threefold) the melatonin secretion. In conclusion, this study has demonstrated that neuropeptide Y modulates the noradrenergic transmission in the rat pineal gland at both presynaptic and postsynaptic levels, using different receptor subtypes and transduction pathways.     

Endocrinology of the Amphibian Pineal

McCord and Allen (1917) found that extracts of mammalian pinealglands contain a potent contracting agent of larval amphibianmelanophores. Lerner and his co-workers determined the chemicalstructure of this principle and named it melatonin. This agentcontracts dermal melanophores at a concentration as low as 10^–10g/ml. Both intact and eyeless larval amphibians blanch whenplaced in the dark, and the melanophore contraction which causesthis lightening response is abolished by pinealectomy. The amphibianpineal contains photoreceptive elements similar to those foundin the vertebrate lateral eyes, and these elements are inhibitedby light but are stimulated in its absence. There is evidencefor the presence of both HIOMT and melatonin the amphibian pineal.It has been proposed that the body-blanching response resultsfrom a direct stimulation of the pineal under conditions ofdarkness leading to a release of melatonin into the generalcirculation which is then responsible for a direct contractingeffect on dermal melanophores. The cytophysiological effectsof melatonin mimic those that take place in the body-blanchingresponse. Since no other hormone or pharmacological agent duplicatesthis response, this is strong evidence that melatonin is a hormonethat normally regulates body blanching. Other evidence for thesupport of this hypothesis is presented. Cytological features of both normal and melatonin-induced lighteningindicate that the effects of melatonin are at the effector celllevel rather than at either the hypothalamus or the pituitary.An inhibition of MSH-release by melatonin is not involved. Melatoninplays a normal role in young larvae to regulate the lighteningresponse that takes place in darkness (the primary chromaticresponse). Neither melatonin nor the pineal play a role in thelater (secondary stage) adaptive background responses of amphibians.As McCord and Allen first noted, the pineal may contain othersubstances which may have other physiological roles in amphibiansas well as other vertebrates. These have been little studied.     

Atypical Teratomas of the Pineal

Atypical teratomas of the pineal were studied pathologically and clinically, and five illustrative cases are described. The results of three postmortem examinations are available, while two of the patients are living, one leading a normal life. Pathological verification revealed that two had suprasellar “ectopic” pinealomas. One neoplasm was located in the pineal (collicular) region. The histology of the tumours was identical, consisting of small cells resembling lymphocytes and large cells with prominent nucleoli and mitoses. This feature plus the midline location led to adoption of the term “atypical teratoma”. Patients with collicular pinealomas presented with headache, vomiting, papilledema, Parinaud''s syndrome and, rarely, nystagmus retractorius. Diabetes insipidus, visual difficulty and hypopituitarism were characteristic features in those with suprasellar neoplasms. Treatment of collicular pinealoma has consisted of the use of a palliative shunt followed by a course of radiation. Chiasmal decompression and radiation have produced favourable results in patients with suprasellar pinealoma.     

Comparative Biochemistry of the Pineal Gland

The pineal gland is biochemically very active. In mammals, ithas the unique capacity to synthesize the hormone melatonin(N-acetyl-5-methoxy-tryptamine). Although the synthesis of melatoninis confined mainly to the pineal gland of all vertebrates, theeyes and brains of amphibians and fish also can form melatonin.Melatonin is synthesized in the pineal as follows: tryptophan 5-hydroxy-tryptophan serotonin N-acetylserotonin melatonin.The final step is catalyzed by the enzyme, hydroxyindole-O-methyltransferase (HIOMT), which is highly localized in the pinealof all vertebrate species examined. The activity of HIOMT ischanged when animals are kept in constant darkness or light.In rats, highest HIOMT activity is present in constant darkness,while the reverse occurs in avian species. In mammals, informationabout lighting reaches the pineal via the retina inferior accessoryoptic tract preganglionic sympathetic fibers superior cervicalganglia postganglionic fibers pineal parenchymal cells. Lightingmessages reach the hen's pineal via a nonretinal pathway. Studieswith tissue culture indicate that noradrenaline liberated fromsympathetic nerves stimulates synthesis of melatonin. Thereare circadian rhythms in pineal serotonin content which areendogenous and abolished by removal of superior cervical gangliaor by decentralization. There is also a 24-hour rhythm in pinealnoradrenaline. This rhythm is exogenous and is abolished byblinding or cutting the inferior accessory optic tract.     

The Effects of Insertions on Mammalian Intrachromosomal Recombination

We examined the effects of insertion mutations on intrachromosomal recombination. A series of mouse L cell lines carrying mutant herpes simplex virus thymidine kinase (tk) heteroalleles was generated; these lines differed in the nature of their insertion mutations. In direct repeat lines with different large insertions in each gene, there was a 20-fold drop in gene conversion rate and only a five-fold drop in crossover rate relative to the analogous rates in lines with small insertions in each gene. Surprisingly, in direct repeat lines carrying the same large insertion in each gene, there was a larger drop in both types of recombination. When intrachromosomal recombination between inverted repeat tk genes with different large insertions was examined, we found that the rate of gene conversion dropped five-fold relative to small insertions, while the rate of crossing over was unaffected. The differential effects on conversion and crossing over imply that gene conversion is more sensitive to insertion mutation size. Finally, the fraction of gene conversions associated with a crossover increased from 2% for inverted repeats with small insertions to 18% for inverted repeats with large insertions. One interpretation of this finding is that during intrachromosomal recombination in mouse cells long conversion tracts are more often associated with crossing over.     

Effects of Polymyxin B on Mammalian Urinary Bladder

Previous reports have demonstrated that large cationic polypeptides (of molecular mass 5,000 daltons or greater) cause an increase in the apical membrane conductance of the rabbit urinary bladder epithelium. This report investigates the effects of the small cationic molecule polymyxin B (PX: a 1,400 dalton antibiotic) on the permeability of the rabbit urinary bladder. The addition of micromolar concentrations of polymyxin B to the luminal solution of the rabbit urinary bladder resulted in an increase in the transepithelial conductance of the bladder. The magnitude of the increase in the conductance was dependent upon the concentration of PX, and the polarity and magnitude of the apical membrane potential. As the apical membrane potential was made more cell interior negative, the larger was the increase in the membrane conductance. This voltage-dependent increase in conductance was an exponential function of the applied voltage, with a negligible increase in conductance occurring when the membrane potential was cell interior positive. Upon changing the membrane voltage from cell interior positive to negative, there was a delay before there was a measurable change in the membrane conductance. The longer the apical membrane was exposed to PX, the more poorly reversible was its effect on the transepithelial conductance, suggesting a toxic effect of PX on this epithelium. Received: 9 May 1996/Revised: 17 July 1996     

卵母细胞在哺乳动物卵巢排卵过程中的决定性作用

哺乳动物卵巢排卵是一个复杂的调控过程。卵泡成熟破裂后,卵母细胞从卵巢中排出。卵泡细胞感受排卵刺激,并诱导卵母细胞减数分裂的恢复及其随后的释放。卵母细胞及其周围颗粒细胞的旁分泌在对此起关键性作用,其中卵母细胞对其释放具有决定性作用。作者先前已经阐述过颗粒细胞在哺乳动物卵巢排卵过程中的调控作用,该文将从卵母细胞的发育及其调控角度重点阐明其在排卵过程中的决定作用,旨在进一步理解哺乳动物卵巢的排卵过程,同时为不孕不育等卵巢疾病的治疗提供重要的研究方向和理论基础。     

Ovine Pineal Indoles: Effects of l-Tryptophan or l-5-Hydroxytryptophan Administration

L-5-Hydroxytryptophan (L-5-HTP) (20 or 200 mg/kg i.p.) but not L-tryptophan (500 mg/kg i.p.) loading substantially increases serum melatonin in sheep. In the present study we examined the effects of these compounds on pineal serotonin and six serotonin metabolites. L-Tryptophan failed to increase 5-hydroxytryptamine (5-HT; serotonin) or any of its metabolites despite a five-fold increase in pineal tryptophan. In contrast, L-5-HTP loading produced a marked increase in pineal 5-HT and its metabolites, including N-acetylserotonin (NAS) and melatonin, indicating that an increased synthesis of melatonin is responsible for the increased serum melatonin concentration after loading with this precursor. No change in pineal indoleamine N-acetyltransferase (NAT) activity was seen. These results are consistent with the suggestion that, during daytime in the sheep, 5-HT availability may limit the production of melatonin.