Atrazine Disrupts the Hypothalamic Control of Pituitary-Ovarian Function

Neuroendrocrine regulation of prolactin release

I am profoundly grateful for the great honor which has been bestowed upon me in recognition of my research efforts. It is a privilege for me to give an account of my search for the hypothalamic regulatory hormones. Since my work on the hypothalamus has extended over 23 years, it will be necessary to give a somewhat simplified version of it and omit reference to studies which did not contribute directly to my main objective, that is, demonstration of hormonal activity in hypothalamic extracts and the purification, isolation, determination of the structures of hypothalamic hormones and their testing in biological and clinical settings. Also, in order to avoid significant overlapping with Dr. Guillemin’s lecture, I will concentrate primarily on the LH-releasing hormone (LH-RH).

https://science.sciencemag.org/content/sci/202/4363/18.full.pdf

Aspects of hypothalamic regulation of the pituitary gland

The present study was undertaken to characterize hormonal and morphological events in 4 day and 5 day rat cycles, in order to test 3 different theories concerning the etiological factors altering follicular phase length in mammals. Three rats were killed at each 2 h interval throughout each cycle type. In addition to organ weight measurements, serum levels of estradiol, progesterone, 20ohydroxypreg-4-en-3-one, LH, FSH and prolactin were assessedin terminal samples. The beginning of uterine intraluminal fluid accumulation coincided with the decline in progesterone levels seen during diestrus, rather than with the rise in estrogen and was delayed 12 h in the 5 day cycle from the time of last estrus. The retention of this fluid during the evening of proestrus was 6 h longer in the 4 day cycling rat. Ovulation occurred earlier in the 5 day cycling rats than in those with a 4 day cycle. No significant differences in the gonadotropins or 2oo-hydroxypreg-4-en-3-one were seen when comparing the 2 types of cycles. Estradiol rose during the night of diestrus I (the same time in the cycle) and was identical in both cycle types. Progesterone was not released on proestrus prior to the LH surge in either type of cycle. However, we did find that progesterone values were higher for a longer period of time throughout diestrus I in 5 day cycles. These data have led us to conclude that the 5 day cycle is due to a prolonged progesterone secretion during the metestrous and diestrous stages of the cycle.

Measurement of Serum Steroid and Gonadotropin Levels and Uterine and Ovarian Variables throughout 4 Day and 5 Day Estrous Cycles in the Rat

The neuroendocrine control of prolactin secretion is unlike that of any other pituitary hormone. It is predominantly inhibited by the hypothalamus and, in the absence of a regulatory feedback hormone, it acts directly in the brain to suppress its own secretion. In addition to this short-loop feedback action in the brain, prolactin has been reported to influence a wide range of other brain functions. There have been few attempts to rationalise why a single hormone might exert such a range of distinct and seemingly unrelated neuroendocrine functions. In this review, we highlight some of the original studies that first characterised the unusual features of prolactin neuroendocrinology, and then attempt to identify areas of new progress and/or controversy. Finally, we discuss a hypothesis that provides a unifying explanation for the pleiotrophic actions of prolactin in the brain.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2826.2008.01736.x

Prolactin: a pleiotropic neuroendocrine hormone.

The present study is based on the fact that rat pituitaries autografted on the kidney lose power to maintain ovarian follicles and interstitium, although luteotropic function is retained or enhanced. In 62 adult, cycling rats the pars distalis was autotransplanted to the kidney immediately after parapharyngeal hypophysectomy In the definitive experimental group of 14 rats (MEm-1) the grafts were re-transplanted after 3 to 4 weeks via the transtemporal route into close relation to the median eminence. Estrous cyclesreturned spontaneously in 13 animals 8 to 68 days later; 7 rats became pregnant. Ovaries, uteri and vaginae were histologically normal save for reduced numbers of follicles and corpora lutea. In another group of 10 rats (MEm-2) grafts were re-transplanted under the median eminence 2 to 3 weeks after the first operation. These were each “primed” later with a short sequence of FSH and LH injections, a treatment of little benefit. Gonadotropin secretion became evident at 11 to 66 days; 3 rats cycle...

Functional restitution of pituitary grafts re-transplanted from kidney to median eminence.

Histocytologic comparisons were made, hy means of the periodic-acid Schiff (PAS) and the aldehyde fuchsin (AF) techniques, between pars distalis autografts on the kidney and similar grafts re-transplanted close to the median eminence. Time intervals from transplantation to autopsy ranged from 1 day to 6 months. Transplants to the kidney are severely damaged by the transfer, the functional parenchyma ofthe established grafts apparently being derived from a thin shell of healthy tissue surroundingthe massive central infarct. Reorganization of the graft is essentially complete after 1 week. Normal cytologic differentiation is promptly lost. Large gonadotrophs (PAS+, AF−)are missing, but smaller ones may be found in significant numbers for 2 to 3 weeks; after thatthey are rarely recognized. Thyrotrophs (PAS +, AF+) are prominent during thefirst week, but older grafts usually contain in this category only a few minute, angular basophilesand occasional vacuolated cells thought to be “thyroidectomy cells.” Small...

Histocytologic changes in grafts of rat pituitary on the kidney and upon retransplantation under the diencephalon.

The possible existence of a hypothalamic humoral substance(s) capable of releasing the ovulating hormone from the adenohypophysis was studied. “Pentobarbital blocked” proestrous rats were used, and the effect on ovulation of various materials was determined upon direct intrapituitary infusion. The substances tested were acid extracts of bovine and rat median eminence tissues, bovine hypothalamic and cortical tissues, arginine-vasopressin, epinephrine, histamine and extraction solvent. Of 34 animals that received the intrapituitary infusion of bovine and rat median eminence extracts, 24 ovulated following the infusion. When bovine extracts were administered intravenously the effective dose had to be increased 10 to 48 times that infused into the pituitary, in order to elicit a response. Twenty-eight animals were used for the intrapituitary infusions of control substances. Only 1 of these animals ovulated following the infusion. Additional controls comprised 10 animals that received only the blocking inject...

Induction of ovulation in rats by direct intrapituitary infusion of median eminence extracts.

The persistence of luteotropin (LTH) secretion in pituitary grafts was studied in 47 rats. In 14 the pars distalis was autografted to the anterior chamber of the eye on the day of estrus. In the 9 animals in which the graft “took,”secretion of LTH was demonstrated. When the pars distalis was autografted to the kidney on various days of the cycle (2 animals on the day of estrus, 7 on the second day of diestrus, 9 on the third day of diestrus and 15 in proestrus), secretion of LTH was found in all cases. This was not at first recognizable in the last group, for luteolysis occurs during proestrus and the corpora lutea had lost their capacity to respond. Once new corpora lutea were produced by gonadotropin injection, LTH secretion was demonstrable. In all cases LTH secretion was indirectly measured through the ability of uteri to respond to trauma with a decidual reaction. Despite the fact that no estrogen secretion was evident in the engrafted rats, uteri retained a reactivity to trauma for as long as 42 day...

Comparative study of luteotropin secretion by hypophysial autotransplants in the rat; effects of site and stages of the estrus cycle.

The effects of hypophysial stalk transection and mechanical stimulation of the hypothalamus on luteotropin (LtH) secretion were compared in 75 female rats. Stalk section, accompanied by an effective barrier to vascular regeneration, brought about continuous secretion of LtH, expressed by a persistent pseudopregnant state (10 rats). Representative animals exhibited a decidual reaction to uterine trauma as late as 74 days postoperatively. When the stalk transection was ineffective, due to faulty placement of the barrier, only a temporary pseudopregnancy ensued and vaginal cycles returned after 8-37 days (15 rats). Simple mechanical stimulation of the median eminence region during vaginal estrus was followed in all cases (11 rats) by temporary pseudopregnancy. On the other hand, cycles were uninterrupted in 10 of 12 animals by comparable manipulation of the temporal lobe. When performed during diestrous day 1, mechanical stimulation of the hypothalamus also resulted in pseudopregnancy (in 5 of 6 animals). Du...

Miroslava Nikitovitch-Winer

Papers

Functional restitution of pituitary grafts re-transplanted from kidney to median eminence.

Histocytologic changes in grafts of rat pituitary on the kidney and upon retransplantation under the diencephalon.

Induction of ovulation in rats by direct intrapituitary infusion of median eminence extracts.

Comparative study of luteotropin secretion by hypophysial autotransplants in the rat; effects of site and stages of the estrus cycle.

Effect of hypophysial stalk transection on luteotropic hormone secretion in the rat.