ABSTRACT

The noradrenergic innervation of the ovary of prepubertal rats causes an inhibitory response of the follicles to gonadotrophins, leading to ovulation. We investigated the possibility that noradrenergic peripheral denervation at birth, produced by treatment with guanethidine, modifies the positive feedback effects of gonadotrophins and oestradiol in prepubertal rats, and also the possibility that peripheral denervation can modify the anovulatory syndrome induced by androgenization at birth.

Noradrenergic peripheral denervated rats of 18 days of age treated with pregnant mare serum gonadotrophin (PMSG) ovulated 96 h later, while normal animals did not ovulate (4/9 vs 0/12, P < 0·05) and the number of ova shed was lower than in rats which ovulated spontaneously at first vaginal oestrus (3·5 ± 0·6 vs 8·3 ± 0·4 (s.e.m.), P < 0·01). Oestradiol benzoate (10 μg) did not induce ovulation in either normal or denervated animals (0/11 and 0/11). The anovulatory syndrome induced by the administration of testosterone propionate (75 μg) at birth was partially blocked by noradrenergic peripheral denervation (4/7 ovulated vs 0/10).

The results suggest that some neural information arising from the ovary modulates, in an inhibitory way, the stimulatory feedback mechanisms required to induce ovulation. Partial inhibition of the anovulatory syndrome resulting from androgenization caused by peripheral noradrenergic denervation suggests that noradrenergic neural information sent by the ovary to the hypothalamus results in a decreased concentration of noradrenaline in the hypothalamus and in the aromatization of androgens to oestrogens.

Journal of Endocrinology (1992) 135, 415–420

ABSTRACT

Anterior pituitary glands were removed from neonatally androgenized (100 μg testosterone propionate) female rats and normal controls at 5, 10, 18, 21, 30, 60 and 90 days of age, and the multiple forms of FSH present within them were separated by chromatofocusing (pH range 7·5–4·0). Additional pituitary glands from intact adult males (90 days old) were also studied for comparative purposes. All animal groups exhibited multiple forms of immunoactive FSH within a pH range of 7·5–4·0, as well as an additional FSH form obtained after the addition of 1·0 mol NaCl/l to the chromatofocusing column (salt peak). In animals 5–30 days old (controls and androgenized) the majority of FSH applied to the chromatofocusing columns was recovered within the salt peak (45-85% of total FSH immunoactivity recovered). However, as the animals aged, more FSH immunoactivity focused within less acidic regions (isoelectric point (pI) 5·9–5·0); pituitaries from animals 60 days old contained the greatest proportion of FSH focused within this pH range (controls, 39·2±0·6%; androgenized, 23·1 ±0·9% of total immunoactivity recovered; P < 0·03 vs animals 30 days old for both experimental groups). This shift towards less acidic FSH was attenuated in androgenized animals compared with the controls (P<0·01).

In control adult rats, the chromatofocusing distribution pattern of pituitary FSH varied according to the day of the oestrous cycle. Pituitary extracts from control rats decapitated during the morning of pro-oestrus, oestrus and day 1 of dioestrus exhibited the highest proportion of immunoactive FSH (23·2–28·8% of total) focused within a pH range of 5·9–5·0, whilst only 10·4–11·6% of FSH from androgenized rats and those on day 1 of dioestrus was recovered within this pH range (P<0·05). In control animals decapitated during the morning of prooestrus and oestrus, 10–26% of FSH focused within the most alkaline region (pI 7·5–6·0); the chromatofocusing pattern of pituitary FSH from the neonatally androgenized animals was characteristic, in that no more than one peak (1·5±0·5% of total) was detected in this alkaline region. In the adult male rats, the majority of pituitary FSH eluted from the chromatofocusing columns within a pH of 4·9–4·0 (52·4±1·2% of total FSH immunoactivity) and the salt peak (pH <4·0) (33·1 ±2·4 of total). All FSH isoforms obtained after chromatofocusing represented α and β dimers as disclosed by size exclusion chromatography.

The results strongly suggest that a cyclic or 'female' pattern of hypothalamic and gonadal secretion leads the anterior pituitary towards the production of less acidic FSH isoforms, whereas a tonic or 'androgenic' type of secretion, as that present in adult males and females with the androgen-induced anovulatory syndrome, leads more to the production of strongly acidic FSH isoforms. The finding of qualitative and quantitative differences among normally cycling and androgenized animals gives further support for the concept of the existence of a sexual dichotomy in terms of the type of FSH synthesized by the anterior pituitary gland.

Journal of Endocrinology (1990) 126, 323–332

To explore endocrine effects in relation to para,para'-dichloro-diphenyl-dichloro ethylene (p,p'-DDE) body burden and past occupational exposure to its precursor dichloro-diphenyl-trichloro ethane (DDT), we assayed serum sex hormones, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17beta-estradiol (E2), testosterone and sex hormone binding globulin (SHBG), and p,p'-DDE levels in 107 male participants in a 1946-1950 anti-malarial campaign in Sardinia, Italy. Cumulative DDT exposure during the anti-malarial operations was retrospectively estimated from detailed reports of the anti-malarial agency. Ortho,para-DDE, and its precursor ortho,para-DDT were always below the detection limit. p,p'-DDT was detected in 14/107 subjects, and p,p'-DDE in 106/107 subjects. The median lipid-adjusted p,p'-DDE serum concentration over the total study population was 396 parts per billion (interquartile range 157-1045), and it did not vary according to the job at the time of anti-malarial operations, nor was it affected by cumulative DDT exposure. LH, FSH, and SHBG, but not testosterone or E2, showed a significant positive correlation with age. Neither current serum p,p'-DDE nor past cumulative DDT exposure affected sex hormone concentrations. Our results suggest that (1) the low current p,p'-DDE serum concentration does not affect serum hormone levels, and (2) past cumulative DDT exposure is not correlated with the current p,p'-DDE serum level, nor does it show persistent effects on serum hormone levels.

This study aimed to determine the relative importance of different functional and morphological pancreatic changes induced by the chronic administration of a sucrose-rich diet (SRD) to maintain normal glucose homeostasis. Male Wistar rats were fed either sucrose (SRD) or starch (CD) for 6 and 12 months. At both periods, serum glucose and triacylglycerol levels were significantly higher (P<0.05; paired and unpaired Student’s t-test) in SRD rats. Serum insulin levels were significantly lower in SRD only at 12 months. At 6 months, the insulin secretion dose–response curve in SRD rats showed a shift to the left that was no longer observed at 12 months, when SRD islets decreased their response to 16 mM glucose. At 6 months, SRD rats showed a significant increase in β-cell volume density (Vvi) and islet cell replication rate, together with a decrease in β-cell apoptotic rate. Changes were not detected in the percentage of PDX-1- and islet neogenesis associated protein (INGAP)-positive cells. Conversely, at 12 months, there was a significant decrease in β-cell Vvi and in the percentage of PDX-1-positive cells; the islet cell replication rate was not modified, and the number of apoptotic β-cells increased significantly. No signs of increased neogenesis or INGAP-positive cells were recorded at any period in SRD rats. Our results show that SRD rats are unable to develop functional and morphological pancreatic reactive changes sufficient to maintain normal glucose and triacylglycerol levels for a long period. Such failure could be ascribed to their inability to increase the rate of neogenesis and of INGAP production.