Harderian Porphyrin Research Articles

Effect of hyperprolactinemia induced by pituitary grafts or castration on porphyrin content of the mouse Harderian gland.

The histology and porphyrin concentrations of Harderian glands and plasma prolactin levels were examined in B6C3F1 mice castrated or isografted with pituitaries in combination with the administration of bromocriptine (2-bromo-á-ergocryptine), a potent suppressor of prolactin. Four pituitaries were transplanted underneath the bilateral kidney capsules of each mouse. Furthermore, we investigated Harderian porphyrins and plasma testosterone levels in mice that were castrated or treated with neuroleptic butyrophenone (timiperone), a potent accelerator of prolactin, and treated concurrently with bromocriptine. Light microscopically, pituitary grafts increased the concretion of porphyrin pigments within the Harderian gland lumina. Pituitary grafts or castration increased both Harderian porphyrin concentrations and plasma prolactin levels compared with the intact control mice. In pituitary-grafted or castrated mice, bromocriptine distinctly prevented the rise in both porphyrins and prolactin levels. Administration of butyrophenone did not result in any marked change in testosterone levels, although Harderian gland porphyrins were significantly increased. The present results indicate that in mice prolactin stimulates the porphyrin production of the Harderian gland and has an important role in the regulation of Harderian gland porphyrins.

Harderian gland function of Indian tropical palm squirrel, Funambulus pennanti.

The Harderian gland (HG) of the Indian palm squirrel, F. pennanti, is composed of acini of a single type of simple columnar cells with uniform-sized lipid droplets and porphyrin (P) in the lumen. Morphologically it presented no sexual dimorphism except for the HG weight which revealed that males are acyclic. Circadian study of Harderian gland porphyrin (HG-P), plasma melatonin, (aMT) and testosterone showed a characteristic two peak cyclicity. In females, HG, HG-P and pineal gland weight, and plasma aMT presented an annual inverse relation. Circadian study in females only exhibited a two peak cyclicity of HG-P, plasma aMT, and estradiol. Pinealectomy (PX) and harderianectomy (HGX) revealed increased HG weight and gonad weight in males. Gonadectomy (GX), on the other hand, had no effect on HG in males. PX in females brought almost a similar effect as noted for males, but HGX had no effect on ovarian weight. GX, interestingly, reduced HG weight and P concentration. Daily evening (4:30-5:00) administration of aMT and 5-methoxytryptamine (5-MT) in males reduced HG weight and HG-P content only in aMT-treated male and female squirrels, thereby suggesting that HG-P is perhaps negatively regulated by pineal gland production and vice versa. Injections of gonadotropin and steroids during the sexually inactive phase showed no effect on HG-P content in both sexes. Short photoperiod (SP) in both sexes stimulated pineal weight without affecting HG weight, while long photoperiod (LP) increased HG-P but reduced the plasma aMT level again without affecting HG-P content. Continuous dark (CD) decreased HG-P, whereas continuous light was ineffective without effecting HG weight in both sexes. In conclusion, HG in this rodent is functionally an important gland having diverse physiological effect in both sexes sometimes with a very clear HG-pineal-gonad relationship.

The Harderian gland: perspectives.

This is the three-hundred and second anniversary of the first description of Harderian glands by Johann Jakob Harder. Despite more than three centuries of study, many features of these glands, including their definition and function, are not yet established to everyone's satisfaction. Some topics of Harderian biology will be reviewed. Morphology, ontogeny: Mammalian Harderian glands secrete largely by exocytosis, which is unusual in a lipid-secreting exocrine gland. Polytubular complexes are features of male hamster glands; their significance is unknown. Porphyrins: High levels of porphyrin in rodent Harderian glands have made this an attractive organ for research on the control of porphyrin synthesis. Attempts to use it as a model of human porphyria, however, have been disappointing. We do not know the function of Harderian porphyrin. The golden (hamster) age: Syrian (golden) hamster Harderian glands show marked sexual differences, including porphyrin levels. This has made them a very useful experimental animal for endocrine studies. The pineal connection: Rodent Harderian glands contain melatonin. Pinealologists often also study Harderian glands, and Harderianologists also often study the pineal. This relationship has contributed valuable insights to our knowledge of both systems. Lipids: Rodent Harderian glands are about 20% lipid by wet weight, and the main secretory product is lipid. The main lipid in many animals is 1-alkyl-2, 3-diacylglycerol. Harderian gland lipid is extensively studied for insights into lipid biochemistry; less has been done on understanding the function of lipids in the physiology of the glands. Behavior: Lipids may function as vehicles for pheromone secretion. In addition, the possible use of Harderian secretion during cold temperatures by gerbils has been noted. Immunology: Bird Harderian glands are probably lymphoid organs. This does not seem to be true of mammals, though the female Syrian hamster shows large numbers of mast cells. Harderian glands of amphibians and reptiles: Research on nonmammalian Harderian glands has been limited, though important insights continue to emerge from these studies.

Lindane and DDT-lnduced changes in rat harderian N-acetyltransferase activity, melatonin levels, and porphyrin concentration

Lindane and DDT-lnduced changes in rat harderian N-acetyltransferase activity, melatonin levels, and porphyrin concentration

Androgenic control of porphyrin in the harderian glands of the male syrian hamster is modulated by the photoperiod, which suggests that the sexual differences in porphyrin concentrations in this gland are important functionally

The porphyrin concentrations of the Harderian glands of Syrian hamsters show marked sexual differences, with male levels being much lower than those of females. Porphyrinogenesis is inhibited by androgens, so orchidectomy leads to elevated male porphyrin concentrations; however, a number of other procedures (some of which also lower androgen levels) prevents this. We studied the effects of short-day photoperiods and melatonin on Harderian porphyrin concentrations. Intact, castrated, or pinealectomized hamsters of both sexes were exposed to long-day or short-day photoperiods. Intact or castrated hamsters were given melatonin injections in the morning or the afternoon, or were given beeswax pellets containing melatonin. After a variable period, Harderian glands were dissected and porphyrins were measured. Prolonged short-day exposure (13 weeks) led to increased Harderian porphyrin concentrations and this rise was prevented by pinealectomy. The rise in Harderian porphyrins following short-day exposure was small, compared with that following castration. Short-day photoperiods also prevented the rise in porphyrin levels associated with castration and this effect was prevented by removal of the pineal. Melatonin injections, whether given in the morning or in the afternoon, had no effect on Harderian porphyrin concentration of castrated male hamsters. Continuous release melatonin pellets reduced the postcastrational rise in porphyrin levels in one experiment, while having no effect in another. In female hamsters, neither short photoperiods nor melatonin pellets influenced Harderian porphyrin concentrations. These results suggested that a factor from the pineal gland helps maintain the low levels of porphyrin which are characteristic of male Harderian glands, despite the decrease in androgen levels which typically results from exposure to short days. Morning and afternoon injections of melatonin and continuous release melatonin pellets failed to resolve the question of whether this pineal factor is melatonin. Our results demonstrated that low male and high female porphyrin levels are maintained in Syrian hamsters, despite seasonal variations in the hormonal milieu, suggesting that these sexual differences are important for the (still unestablished) function of the Harderian glands in this species.

Porphyrin metabolism in the harderian glands of Syrian hamsters: in vivo regulation by testicular hormones, lighting conditions, pineal gland, and pituitary hormones.

The porphyrin concentration in the harderian glands of male hamsters subjected to several endocrine manipulations was studied. Prolonged bilateral gonadectomy resulted in a marked increase in harderian porphyrin concentration. This change was not prevented by either pinealectomy or by constant white light exposure. Castrated hamsters exposed to constant red light showed higher porphyrin concentrations than castrated hamsters kept under white light. Among several hormones studied, serum luteinizing hormone and thyroid-stimulating hormone levels were unexpectedly higher in the constant red light exposed group than in the other groups. In order to test whether luteinizing hormone was involved in the postcastrational rise in harderian porphyrins, we administered a potent luteinizing hormone-releasing hormone (LHRH) agonist. The chronic administration of the LHRH agonist resulted in a decrease in serum luteinizing hormone (because it desensitized the LHRH receptors on the gonadotropes) and, consequently, in serum testosterone levels. However, no rise in harderian porphyrin was observed. It is concluded that the absence of testicular hormones might not be the triggering factor involved in harderian porphyrogenesis.

Hypophysectomy prevents the castration-induced increase in porphyrin concentrations in the harderian glands of the male golden hamster: a possible role for prolactin.

The Harderian glands of golden hamsters contain high concentrations of porphyrin pigments, with female hamsters having considerably higher porphyrin concentrations than males. Castration of male hamsters leads to a rapid increase in porphyrin concentrations; testosterone treatment of females has the opposite effect, suggesting a central role for androgens in inhibiting the realization of high porphyrin concentrations by this organ. Previous studies in our laboratories have shown, however, that administration of a dopamine agonist to castrated hamsters prevents the normal increase in Harderian porphyrins from occurring. This suggests that prolactin is necessary for low androgen levels to lead to maximal increases in Harderian porphyrin concentrations. The present study tested the hypothesis that prolactin is involved in the control of Harderian porphyrin levels in the golden hamster. Although hypophysectomy of male hamsters reduced serum testosterone to levels in castrated hamsters, the resultant increase in Harderian porphyrin concentrations was much less than that seen after a similar period of castration. Furthermore, combining the two procedures (castration and hypophysectomy) also led to a blunted increase in Harderian porphyrin, suggesting that a pituitary hormone is necessary for low testosterone levels to lead to increased porphyrins. Evidence that this pituitary hormone is prolactin comes from the observations that eliminating all pituitary hormones except prolactin, by severing the connection of the pituitary with the hypothalamus or transplanting the pituitary to a distant site (beneath the kidney capsule) led to greatly augmented Harderian porphyrin levels, in intact or castrated male hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

Female syrian hamster harderian gland: Development and effects of high environmental temperature and melatonin injections on histology and porphyrin deposits

We have investigated the development of the Harderian glands of female Syrian hamsters from birth to 8 months of age. The effects of melatonin injections on Harderian gland histology and porphyrin deposits of female hamsters exposed to two different temperatures were also studied. The morphology of the Harderian glands from 30-day-old female hamsters resembled those of sexually mature adult animals. The intraluminal area occupied by porphyrins increased significantly between 20 to 30 days of age. However, the relative number of mast cells per mm2 rose between 30 to 90 days. Both porphyrins and mast cell numbers appeared clearly reduced in the 8-month-old group. Secretory cells characterized by large lipid droplets (type II cells) were not observed. Daily afternoon injections of 25 micrograms of melatonin to female hamsters exposed to 22 degrees C for 14 weeks resulted in the discontinuity of estrous cyclicity, a marked decrease in the intraluminal area occupied by porphyrins, a reduction of the number of mast cells per mm2, and in a marked augmentation of the number of type II cells per mm2. Although the administration of similar dosages of melatonin to hamsters exposed to an environmental temperature of 32 degrees C did not interrupt estrous cycles, a clear reduction of the area occupied by porphyrins was observed. However, the number of mast cells and type II cells per mm2 was unaffected in these animals. Our results suggest that hormones other than ovarian steroids are involved in the regulation of the female hamster Harderian glands. The possible role of melatonin on Harderian gland metabolism is discussed.

Gender differences and time course of castration-induced changes in porphyrins, indoles, and proteins in the Harderian glands of the Syrian hamster

Sexual differences and the effects of orchidectomy were determined for porphyrin and melatonin concentrations and for the activities of the enzymes N-acetyltransferase and hydroxyindole-O-methyltransferase, which synthesize melatonin from serotonin, in the Harderian glands of the Syrian hamster. Porphyrin concentrations in intact males were about 1/400th those of intact females. Castration for 1 week increased male Harderian porphyrin concentrations 10-fold; by 3 weeks, castrated male porphyrin levels were 140 times those of control values. N-Acetyltransferase activity in intact male Harderian glands was about 4 times that of females. Castration led to a drop in N-acetyltransferase activity to female levels within 2 weeks. Hydroxyindole-O-methyltransferase activity was 7 times higher in females than in males and castration had no effect on male Harderian hydroxyindole-O-methyltransferase activity. Neither gender nor castration influenced Harderian melatonin concentrations. Soluble proteins in Harderian glands from male and female hamsters and from male hamsters castrated for 1 and 4 weeks were examined by sodium dodecyl sulfate--polyacrylamide gel electrophoresis. The gel profiles revealed several differences among the protein distribution in male and female gland lysates. Orchidectomy led to a female protein pattern within 4 weeks.

Inhibition of Sα‐reductase does not simulate the effects of androgen deprivation on porphyrin metabolism by Harderian glands from the male Syrian hamster

As 5 alpha-reductase is involved in the metabolism of indolamines in the Harderian glands of Syrian hamsters, we have compared the effects of androgen deprivation and the administration of the potent 5 alpha-reductase inhibitor N,N-diethyl-4-methoxy-3-oxo-4-aza-5-androstene-17-carboxamida on Harderian porphyrin metabolism. Ten days after castration, porphyrin levels had increased to 40 times the values of intact hamsters. However, the inhibition of 5 alpha-reductase, which resulted in a significant decrease in the weight of accessory sex glands, did not modify porphyrin concentrations within the Harderian glands. It is concluded that, contrary to the situation for indolamine metabolism, testosterone per se is the main androgen involved in the sexual differences observed in Harderian porphyrin metabolism.

Bromocriptine prevents the castration-induced rise in porphyrin concentration in the harderian glands of the male Syrian hamster, Mesocricetus auratus.

The Harderian glands in Syrian hamsters exhibit a striking sexual dimorphism. Male Harderian glands show two cell types and low levels of porphyrins and melatonin. Of the enzymes involved in the synthesis of melatonin, N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) show high and low activity levels, respectively. Female Harderian glands show but one cell type and have high porphyrin and melatonin levels, low NAT activity, and high HIOMT activity. In castrated males, the Harderian glands exhibit a female pattern of morphology, porphyrin levels, and indoleamine metabolism. In an attempt to determine whether prolactin in involved in this sexually dimorphic response of the Harderian glands, intact and castrated male and intact female hamsters were injected daily with 500 micrograms of bromocriptine, a dopamine agonist. Bromocriptine led to reduced serum prolactin levels in all groups. It had no apparent effect on the Harderian glands of intact males. In contrast, in castrated males bromocriptine prevented the postcastrational rise in porphyrin levels but had no effect on NAT or HIOMT activities. In females, bromocriptine treatment had no effect on porphyrin concentrations or HIOMT activity; it led to a statistically significant increase in NAT activity. We propose that testosterone inhibits Harderian porphyrin synthesis while dopamine or prolactin stimulates it.

Harderian glands of golden hamsters: morphological and biochemical responses to thyroid hormones

Manipulation of circulating levels of thyroid hormones modifies Harderian gland structure and porphyrin concentrations in male and female golden hamsters. Specifically, thyroxine (T4) and triiodothyronine (T3) induce the morphological conversion of the Harderian glands of females to approximate those of the male. Further, porphyrin concentrations are markedly decreased by this treatment. This effect occurs in ovariectomized animals as well, indicating that the gonads are not involved. Suppression of thyroid function by potassium perchlorate (KClO4) drastically reduces Harderian gland weight in both males and females. However, KClO4 decreases porphyrin levels in the Harderian glands of females and increases it in the male. Concurrently, KClO4 also induces a morphological conversion of the Harderian glands of males to the female type. This effect is evident in photoperiods of either 14:10 (h) or 8:16 (h).