G. F. X. David

Bioavailability of progesterone enhanced by intranasal spraying

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.

Testosterone, cortisol, prolactin and bioactive luteinizing hormone in day and night samples of cerebrospinal fluid and serum of male rhesus monkeys

Testosterone (T), cortisol (C), prolactin (PRL) and bioactive luteinizing hormone (bLH) were found to be normal constituents of the cerebrospinal fluid (CSF) of all the 15 adult male rhesus monkeys studied. The CSF levels of the hormones showed a good correlation with their serum levels. The geometric mean values of circulating levels of T, PRL, bLH in all the animals studied were significantly lower in the samples of the two body fluids collected between 09.00 and 11.00 h as compared with those collected between 21.00 and 23.00 h. C levels were higher during the day as compared with the night samples. This marked difference between the day and night levels of the circulating hormones was not observed in a few individuals which suggests that the diurnal changes in circulating levels of these hormones may not occur as a rule in all rhesus monkeys. The serum:CSF ratios for C, PRL and bLH did not vary significantly between the day and night samples of the body fluids as they did for T. This suggests that T is poorly transferred from the blood to the CSF as compared with the other 3 hormones studied. The possible pathways by which the hormones are transferred into the CSF and the functional significance of their presence in the CSF are discussed.

Histochemical localization of cholinesterases in the neural tissue of the pineal in the rhesus monkey

The neural tissue of the monkey pineal contains both acetyl and butyryl cholinesterases. Acetylcholinesterase was localized in the cisternae of the nuclear membrane, rough endoplasmic reticulum, on the plasma membrane of the neurones, and on the axolemma of both non-myelinated and myelinated fibres. The enzyme was not found in the axosomatic or axo-dendritic synapses. It is therefore suggested that the pineal neurones have a cholinergic function rather than a cholinoceptive one.

Transfer of Steroidal Hormones from Blood to the Cerebrospinal Fluid in the Rhesus Monkey

Rhesus monkeys were injected intravenously with tritium-labeled testosterone (T), progesterone (P), 17 α -hydroxyprogesterone (17 OHP), norethynodrel (N) and mestranol (M) to determin

A New Approach to Fertility Regulation by Interfering with Neuroendocrine Pathways1

Recent findings that may lend themselves to the development of an alternative method of neurohormonal fertility regulation are discussed particularly the mechanism whereby the endocrine functions of the ovary and adenohypophysis are integrated. Anatomically the tanycyte ependyma of the hypothalamic 3rd ventricle and other cells of the same region that show cytoplasmic granules reflective of the reproductive-hormonal status may be directly involved in regulation of pituitary gonadotropins. The habenular ependyma has also been implicated along with the pineal which may be a 2nd site of pituitary-gonadal integration. Physiologically a study in rhesus monkeys has found the uptaker of steroids into the cerebrospinal fluid (CSF) to be more complete when thy are administred intranasally rather than intravenously. If the CSF serves as a humoral pathway to the different regions of the brain and if it s more accessible via the intranasal route these facts sould lead to fertility control at the ventricular level of the brain.

Seminal fructose in normal and infertile men

Fructose levels and fructolysis index in human semen were analysed to assess a correlation, if any, between the levels of this glycolysable sugar and sperm concentration. Semen was collected from normospermic men and men with azoospermia or oligospermia. Seminal fructose levels were elevated in men with obstructive azoospermia and in men who remained azoospermic following vasoepididy mostomy done to correct epididymal blockage. Men with sperm concentration of less than 20 million/ml pre-operatively or following vasoepididy mostomy, showed significantly high levels of fructose and lower fructolysis index. Fructose levels in normospermic infertile men, as well as in men with normal sperm counts (more than 20 million/ml), were similar to that in men of proven fertility.

Circadian and circannual changes in the testicular function of adult rhesus monkeys

The endocrine and gametogenic status of the testes were studied in 9 healthy adult rhesus monkeys of proven fertility throughout a one-year period. Testosterone levels were estimated by radioimmunoassay in blood samples collected at 4 h intervals over a 24 h period once a month. Semen samples and testicular biopsies were also examined once a month. A well-defined circandian rhythm was evident in serum levels of testosterone. The rhythmicity was less pronounced in February and September. The 24 h mean levels of serum testosterone were high between the months of August to March and low in the months of May to July. All animals did not uniformly respond to electro-ejaculation in April and May. Semen volume and total number of spermatozoa were maximal between September and March and least from April to August. Testicular biopsies indicated that all stages of spermatogenesis were evident between September and March and the spermatogenic activity was less evident between April and August. The contents of Sertoli cells showed a seasonal cyclicity; they were laden with lipid droplets during April to August when spermatogenesis was quiescent and vacuolated during September to March when spermatogenesis was active. These studies indicate that the testing of contraceptive drugs needs to be restricted to months of September to March in male rhesus monkeys otherwise, it is possible that the naturally occurring reproductive quiscence may be attributed to the effect of the drug being tested. The data accrued from the present studies also provide quantitative information on circulating levels of testosterone which could be used as a reference background while evaluating the contraceptive drug-effects in male rhesus monkeys.

Reproductive endocrine effects of intranasal administration of norethisterone (NET) to women

Four consecutive menstrual cycles were studied in six healthy parous women. A solvent mixture comprising propylene glycol:ethanol:water (3:3:4) was sprayed intranasally daily using a glass atomizer between days 5 and 24 of the first (control) menstrual cycle. NET was dissolved in the solvent and similarly administered at a daily dose of 100 mcg during the second and third menstrual cycles. Nasal sprays were not administered during the fourth post-treatment cycle. Blood samples were taken during four consecutive cycles between days 8 and 15 and again between days 20 and 24 of the cycle to estimate levels of estradiol (E2), FSH, LH and progesterone (P). These studies revealed that nasal sprays of NET were well accepted and that no adverse clinical effects or menstrual disturbances occurred. NET inhibited ovulation in one cycle. The E2-induced mid-cycle rise in FSH and LH was either suppressed or inhibited in nine out of the 12 treated cycles. P levels in three treated cycles were indicative of luteal inadequacy. These endocrine effects of NET persisted into the post-treatment cycle in two cases.