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P. Kannisto, Ch. Owman, and B. Walles

Summary. Immature female rats were primed with 4 i.u. PMSG at 08:00 h of Day 26. This results in ovulation in the morning of Day 29. The number of ovulations was counted in terms of newly formed corpora lutea in the morning of Day 30. Various adrenergic drugs were delivered into the ovarian bursa bilaterally in the afternoon of Day 27 to study their effect on ovulation. A methyl cellulose gel solution was used as vehicle to minimize leakage from the bursa. Noradrenaline, terbutaline and 4-aminopyridine significantly enhanced the number of corpora lutea compared to control ovaries injected with gel vehicle alone. The effect of terbutaline was counteracted by propranolol. Phentolamine partly blocked the noradrenaline-induced enhancement and the antagonist alone significantly reduced the number of ovulations. The results indicate that stimulation of α-adrenergic receptors (probably via actions in the follicle wall) as well as β-receptors (influencing steroid-producing cells) may interfere with the ovulation process.

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The trigonum area of the bladder—including the bladder neck and the proximal urethra—of rats and guinea-pigs contains large amounts of noradrenaline. This is consistent with a rich adrenergic innervation of the smooth musculature, particularly in the internal sphincter of the bladder. The innervation is not reduced by hypogastric denervation, indicating that it originates from peripheral ganglia (i.e. short adrenergic neurons). Stimulation of the hypogastric nerves produces seminal emission into the proximal urethra. After hypogastric denervation, there is a seminal reflux into the bladder whether copulation has occurred or not.

Extensive presacral operative dissection in male patients usually results in seminal reflux into the bladder. The excised tissues often contain adrenergic ganglion formations, probably identical with the short adrenergic neurons.

It is suggested that removal of these ganglia, or their more proximal sympathetic input, results in permanent motor deficiency of the smooth musculature in the structures engaged in the emission mechanism, including the bladder neck. This results in a continuous seminal reflux into the bladder (whether coitus occurs or not) due to a continuous slow transport of seminal fluid through the vas deferens as a consequence of persisting segmental contraction and continuous secretion from the accessory genital glands.

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G. Schmidt, Ch. Owman, and N.-O. Sjöberg

Summary. Ovulatory effects of histamine and specific antagonists were studied in isolated perfused ovaries from immature rats treated with 10 i.u. PMSG to stimulate follicular growth and maturation. Histamine alone, like LH, induced ovulation in all ovaries tested, but the number of follicular ruptures was lower after histamine (7·0 and 2·2 ruptures, respectively, per ovary). The histamine-induced ovulations could be inhibited dose-dependently by the H1-receptor antagonist, pyrilamine, or the H2-antagonists, cimetidine and ranitidine. At the concentrations tested, these antagonists did not, when given separately, reduce the LH-induced ovulations significantly, but pyrilamine and cimetidine in combination lowered the ovulation frequency by 65%. The prostaglandin synthesis inhibitor, indomethacin, was not able to block the histamine-induced ovulations.

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G. Schmidt, Ch. Owman, and N.-O. Sjöberg

Summary. Mast cells, visualized with toluidine blue staining and the Falck-Hillarp fluorescence technique, were mainly located around large blood vessels in the hilus region of the ovary in adult rats and in immature rats treated with PMSG. Histamine concentration in the rat ovary was significantly reduced after the LH surge in PMSGtreated animals, corresponding to a reduced number of ovarian mast cells. No marked change in the number of mast cells and histamine concentration was found in adult rats during the oestrous cycle. Histamine as well as the H1-agonist, 2-methylhistamine, and the H2-agonist, 4-methylhistamine, induced ovulations in the isolated perfused rat ovary. Ovulation rates were significantly lower than those evoked by LH. The histamine liberator, Compound 48/80, induced ovulations which were blocked by the combined effect of the H1- and H2-histamine receptor antagonists, cimetidine and pyrilamine. The anti-degranulating agent, disodium cromoglycate, did not block ovulations induced by Compound 48/80.

The results show that the level of ovarian histamine, which is primarily stored in mast cells, can be influenced by PMSG treatment, and that the amine is able to induce ovulations in gonadotrophin-primed rats by an effect mediated by both H1 and H2 receptors.

Keywords: histamine; ovary; in vitro; ovulation

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G. Helm, Ch. Owman, N.-O. Sjöberg, and B. Walles

Summary. The contractile pattern of the human Fallopian tube was studied in preparations from the ampullary and isthmic regions mounted in an organ bath for measurement of longitudinal and circular smooth muscle activity. The material was obtained during the follicular, ovulatory, and luteal phases of the cycle as defined primarily from plasma oestrogen and progesterone values. The frequency of the spontaneous contractions increased progressively during the follicular phase to become maximal around ovulation. There was no consistent difference between isthmus and ampulla; the circular musculature had a higher frequency than the longitudinal during the ovulatory phase. Noradrenaline (3 × 10−6 M) in general potentiated the difference in frequency seen between the ovulatory phase on the one hand and the follicular and luteal phases on the other. Contractile activity, assessed by planimetric integration of the curve on the pen-recorder trace, increased markedly during the ovulatory phase in all types of smooth muscle preparations. Exogenous noradrenaline inhibited spontaneous motor activity in preparations from pregnant or post-menopausal women or from women taking combined-type oral contraceptives. This effect was most marked in the circular muscle. Thus the different regions of the human Fallopian tube in vitro show various patterns of spontaneous motor activity in relation to the plasma steroid concentrations during the menstrual cycle. Responses to exogenous noradrenaline also varied, indicating that the effects of endogenous noradrenaline released from sympathetic nerves may vary similarly.

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Departments of Histology, Obstetrics and Gynecology and Zoology, University of Lund, S-223 62 Lund, Sweden

(Received 16th June 1975)

Fluorescence histochemistry has shown that the human ovary is extensively supplied by adrenergic nerves, many of which are not associated with blood vessels and run in close contact with the follicles in a manner suggesting a local innervation (Owman, Rosengren & Sjöberg, 1967). Particular attention has been paid to these adrenergic nerves since it became established by electron microscopy that the theca externa of the follicle contains smooth muscle cells (Okamura, Virutamasen, Wright & Wallach, 1972). In order to elucidate whether the smooth musculature is involved in the contractility of the Graafian follicle, and whether neurogenic mechanisms can influence this function, a study was performed on material obtained from 32—48-year-old patients undergoing abdominal hysterectomy because of pains, bleeding, uterine myoma, or preinvasive carcinoma of the cervix. The follicles were dissected out,

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S. Batra, Ch. Owman, N.-O. Sjöberg, and G. Thorbert

Summary. Plasma oestradiol concentrations did not change during hCG-induced pseudopregnancy except for a slight increase on Day 18. However, a marked decline was observed in tissue oestradiol on Day 3 whether expressed on the basis of tissue wet weight or protein. The lowest concentration was found at Day 6 but the Day 18 values were comparable to those of untreated controls.

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G. Schmidt, J. Jörgensen, P. Kannisto, F. Liedberg, B. Ottesen, and Ch. Owman

Summary. The immature rat ovary contains VIP immunoreactive nerve fibres sparsely distributed around blood vessels, in the interstitial gland and around follicles. The VIP concentration, measured radioimmunologically, decreased significantly after PMSG treatment (10 i.u.), probably due to ovarian enlargement and oedema, while the total VIP content (total of 0·12 pmol in both ovaries) did not change after PMSG priming. The ovulatory effect of VIP was studied using in-vitro perfused ovaries from immature 28-day-old rats primed with 10i.u. PMSG. In all ovaries perfused, VIP (10−7 m) induced ovulations with a rate of 2·33 ± 0·56. The ovulation rate was significantly lower than that of ovaries stimulated by LH (0·1 μg/ml) (5·20 ± 0·86 ovulations per ovary). No synergistic effect on the ovulation rate was seen when LH and VIP were administered together (5·20 ± 0·49 ovulations per ovary). The results suggest that the neuropeptide VIP may represent one of the local factors involved in the ovulation process.

Keywords: VIP; rat ovary; ovulation

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B. Walles, Ute Gröschel-Stewart, Ch. Owman, N.-O. Sjöberg, and K. Unsicker

Summary. Contractile proteins (actin and myosin detected by immunohistochemistry) were present in elongated cells forming concentric layers in the theca externa of Graafian follicles and around corpora lutea. Immunofluorescent cells were also found in the ovarian stroma. Study of adrenergic nerve fibres by the glyoxylic acid technique showed numerous branches in between and in close association with the contractile cells.