Androgenic control of epididymal function in rhesus monkey and rabbit.

The effects of castration and testosterone replacement therapy on the histology and biochemical composition (RNA, DNA, total protein, alkaline phosphatase, acid phosphatase, hyaluronidase, sialic acid, glycogen, phospholipids, and glycerylphosphorylcholine [GPC]) of the epididymis of the rabbit and rhesus monkey were investigated. Castration produced marked ponderal, histologic, and biochemical changes in the epididymis. In the androgen-deficient state the tubular diameter and epithelial cell height were reduced and there was an increase in interbular stroma. The levels of RNA, DNA, phospholipids, and GPC were also reduced in castrated animals. Testosterone treatment restored the histologic features and the levels of various biochemical constituents to a great extent but not to the intact control level. The importance of endocrine and exocrine factors of the testis in relation to epididymal function is discussed.

Functional maturation of the epididymis in rabbit and rhesus monkey.

The changes in the weight, histology and biochemical composition of the epididymis (caput, corpus and cauda segments) in prepuberal rabbit and rhesus monkey in response to testosterone treatment were investigated. The increase in the weight of the organ was accompanied by increased levels of RNA and DNA. Androgen therapy caused an increase in the concentration of sialic acid, phospholipids and glycerylphosphorylcholine and activities of alkaline phosphatase, acid phosphatase and hyaluronidase. The cauda region of the epididymis exhibited relatively higher levels of sialic acid and glycerylphosphorylcholine. These findings are discussed in relation to the functional maturation of the organ and the role of androgen in this process.

Effect of normal and defective vasectomy on the urinary 17-ketosteroid excretion rate and total pituitary gonadotrophin content in dogs.

PIP: The effect of normal and defective vasectomy on the urinary excretion rate of 17-ketosteroids and total pituitary gonadotropin levels were studied in the dog. The urinary excretion rates were not markedly changed at 90, 180, and 360 days after the operation, though there was a transitory, but significant (p less than .05-.01), increase at 15 days. Pituitary gonadotropin content was higher in vasectomized animals than controls, but was not markedly different among the different forms of vasectomy performed. There did not appear to be any correlation of the different vasectomy procedures with urinary 17-ketost eroid excretion or pituitary gonadotropin content.^ieng

Antifertility agents. 12. Structure-activity relationship of 3,4-diphenylchromenes and -chromans.

Synthesis and antiimplantation activity of variously substituted 2,2-dialkyl-3,4-diphenylchromenes and 3,4-cis- and trans-chromans derived from them are described. Pregnancy-inhibiting activity in rats was exhibited by a number of these compounds, which was particularly marked in the case of 3,4-trans-3-phenyl-4-p-(beta-pyrrolidinoethoxy)-phenyl-7-methoxychroman (32), the corresponding 2,2-dimethyl analog 34, and 3-phenyl-4-p-(beta-pyrrolidinoethoxy)phenyl-7-methoxychromene (26). The structure-activity relationship of these compounds is discussed.

Effect of 3,4-trans-2,2-dimethyl-3-phenyl-4-P-(beta-pyrrolidinoethoxy) phenyl -7-methoxy chroman (centchroman) on the biochemistry of the fallopian tube and uterus of rhesus monkeys (Macaca mulatta).

PIP: The biochemical effects of the nonsteroidal compound Centchroman were observed in healthy, adult, female rhesus monkeys. The compound was administered at the antifertility dose (.625 mg/kg) for 22 days in a cycle. No marked weight changes were seen in the Fallopian tube, ovary, adrenal or pituitary as a result of treatment. Uterine weight increased significantly, however (p less than .01). In the Fallopian tube, levels of glycogen and protein increased significantly (p less than .01), lactic acid decreased significantly (p less than .01), and nonprotein nitrogen was unchanged as a result of treatment. Similar changes were observed in the uterus, and in addition, total total phospholipid concentration rose significantly (p less than .01) in the uterus. The activities of beta-glucuronidase, acid and alkaline phosphatases and glucose-6-phosphate dehydrogenase (G-6-PD) in the Fallopian tube were unchanged due to treatment. Adenosine triphosphatase (ATPase) and malic dehydrogenase activities were significantly stimulated (p less than .01) and lactic dehydrogenase activity was significantly depressed (p less than .01). In the uterus, beta-glucuronidase and acid and alkaline phosphatase activity were unaltered, however, the activities of ATPase and the dehydrogenases of glucose-6-phosphate, lactate and malate were markedly increased (p less than .01). It is suggested that the antifertility effect of Centchroman may be due principally to the ability of the compound to elicit estrogen-like responses in the Fallopian tube and uterus.^ieng

Effect of 2-phenyl-3-p-(beta-pyrrolidinoethoxy) phenyl-beta-methoxy benzofuran hydrochloride (DBF) on the biochemistry of the fallopian tube and uterus of rhesus monkey (Macaca mulatta).

PIP: The effects of the nonsteroidal title compound (DBF) on the biochemical composition of the Fallopian tube and uterus were studied in the rhesus monkey. Monkeys received 2 mg/kg daily by mouth, which is the antifertility dose. The weight of the pituitary was significantly decreased (p less than .05) due to treatment, but the weights of the Fallopian tube, uterus, ovary and adrenal were unaltered. In both the Fallopian tube and uterus, DBF induced a significant increase (p less than .01) in the concentration of glycogen, protein and nonprotein nitrogen, and a significant decrease (p less than .01) in the concentration of lactic acid. The total phospholipid level in the uterus showed an increase (p less than .01) in the activities of adenasine triphosphatase (ATPase), malic dehydrogenase, acid and alkaline phosphatases, and glucose-6-phosphate dehydrogenase (G-6-PD) was seen. Lactic dehydrogenase activity fell (p less than .01) and the activity of beta-glucuronidase was unchanged. In the uterus, ATPase, malic dehydrogenase, alkaline phosphatase and lactic dehydrogenase activities increased significantly (p less than .01), beta-glucuronidase and acid phosphatase activities fell (p less than .01) and G-6-PD activity was unaltered. The antifertility effect of DBF may be due to its ability to elicit many biochemical effects similar to those induced by a typical estrogen.^ieng

Effect of a copper intrauterine contraceptive device and nylon suture on the estradiol 17beta-6, 7-H3 and progesterone 1, 2-H3 in the rat uterus.

PIP: Copper wire or nylon suture was inserted in 1 horn of rats and their uterin were subsequently studied to determined the effect of these IUDs on in vitro estradiol-17beta, 6,7-tritiated and progesterone 1,2-tritiated. Control horns took up significancy more (p .01) estradiol than either copper or nylon IUD-fitted horns. The copper IUD horn showed an increase (p .01) in progesterone uptake while the nylon IUD horn showed a decrease (p .01) in progesterone uptake. The estrogen to progesterone ratio in uptake of the control and IUD horn of the nylon IUD-fitted rats had significantly less (p .01) uptake of both progesterone and estradiol compared to either copper or nylon IUD-fitted rats.^ieng

The effect of efferent duct ligation on the uptake of 65-ZN by the epididymis and vas deferens of rhesus monkeys (Macaca mulatta).

PIP: A study dealing with the uptake of zinc-65 by different segments of the epididymis and vas deferens of the rhesus monkey (Macaca mulatta) in the presence or absence of spermatozoa is reported. It was determined that zinc-65 uptake by the vas deferens of the control side was significantly higher than that of the epididymal segments (vas deferens vs. caput, proximal and distal corpus, or cauda, p less than .01). Amon g the epididymal segments themselves there was no significant difference . Efferent duct ligation consistently reduced the uptake of zinc-65 in all portions of the epididymis and vas deferens (control vs. ligated: caput, corpus, cauda, and vas, p less than .01). The percentage reduction in the uptake by different segments of the epididymis and vas remained virtually constant in the ligated side (caput, 57%; proximal corpus, 53%; distal corpus, 64%; cauda, 55%; vas deferens, 55%). Nevertheless, zinc-65 uptake by vas continued to be significantly greater than that of the epididymis. It is noted that the reduced zinc-65 accumulated on the ligated side could at least be partly due to absence of spermatozoa. It is further suggested that the lowered uptake of zinc-65 by the epididymis and vas deferens following efferent duct ligation in the monkey may be also due to a local androgen deficiency.^ieng

Effect of intravaginal instillation of some non-steroidal oral antifertility agents on pregnancy in rats.

PIP: A study was conducted of the effect of intravaginal instillation of 3 nonsteroidal oran antifertility agents in pregnant rats. The 3 compounds used were 2-phenyl-3-rho-beta-pyrrolidinoethoxyphenyl-6-methox y benzofuran hydrochoride (DBF), 20 mg/kg; 2-phenyl-3-rho-beta-pyrrolidi noethoxyphenyl-naptha (2:1,b furan (NF), 10 mg/kg; and Centchroman, 1.25 mg/kg. These agents were administered on Day 1 postcoitum at the single-day oral contraceptive dose. Control animals were inserted with a pellet containing only carboxymethyl cellulose. Only Centchroman was 100% effective in preventing pregnancy. Even at half the normal dose, Centchroman was effective. Of the 3 compounds, only Centchroman has an antiprogestational property which may be contributing to Centchroman's high antifertility activity by the vaginal route and may prevent side effects.^ieng